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Zhang HW, Chang GD, Liu XM, Gao H, Xu XD, Lv SY. Analysis of epidemiological characteristics and psychopsychological factors of arrhythmia in the elderly. World J Psychiatry 2025; 15:100281. [DOI: 10.5498/wjp.v15.i4.100281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/16/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Irregular heart rhythms are a primary manifestation of cardiovascular disease, considerably contributing to global morbidity and mortality rates. Moreover, patients with cardiac arrhythmias often experience a higher prevalence of sleep disorders, anxiety, and depression owing to various factors.
AIM To investigate the epidemiological characteristics and psychological factors associated with arrhythmia in the elderly and to establish a theoretical foundation for its prevention and treatment in older adults.
METHODS A retrospective analysis was performed on 169 elderly patients admitted to the Shangqiu First People’s Hospital from December 2022 to December 2023. All subjects underwent 24-hour electrocardiogram monitoring to record heart rate, heart rate variability, and 24-hour ambulatory electrocardiogram data. Additionally, patients’ medical records were reviewed to gather information on their general condition, including age, gender, underlying diseases, and other relevant factors. Patients were divided into four groups based on their Hamilton Anxiety (HAMA) and Hamilton Depression Rating Scale (HAMD) scores: Group A (HAMA scores ≥ 7), Group B (HAMD scores ≥ 7), Group C (both HAMA and HAMD scores ≥ 7), and Group D (HAMA and HAMD scores < 7). Psychological factors such as depression, anxiety, sleep status, and quality of life were analyzed. Pearson correlation was used to examine the relationship between scores from the Pittsburgh Sleep Quality Index (PSQI), HAMA/HAMD scales, and the Short Form 36-item Health Survey (SF-36) with the presence of arrhythmia.
RESULTS Among the 169 patients, 87 (51.5%) had concurrent arrhythmia. Atrial arrhythmias constituted the largest proportion at 34.8% (30 out of 87), followed by sinus tachycardia at 24.1% (21 out of 87), and ventricular arrhythmias at 9.2% (8 out of 87). Factors such as advanced age, coronary heart disease, hypertension, smoking, exposure to secondhand smoke, and residing in rural areas significantly increased the risk of developing arrhythmia. There was a statistically significant difference between the two groups regarding PSQI, HAMA-14, HAMD-17, and SF-36 scores. Pearson correlation analysis revealed that PSQI, HAMA-14, and HAMD-17 scores were positively correlated with arrhythmia in the elderly, while the SF-36 score was negatively correlated. The anxiety, depression, and combined anxiety–depression groups exhibited significantly higher PSQI, HAMA-14, and HAMD-17 scores compared to the nonanxiety and non-depression group.
CONCLUSION Arrhythmia among the elderly is primarily found in individuals with advanced age and existing health conditions. It is also linked to psychological factors such as depression, anxiety, reduced quality of life, and sleep disturbances.
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Affiliation(s)
- Hong-Wei Zhang
- Department of Arrhythmia, Shangqiu First People’s Hospital, Shangqiu 476100, Henan Province, China
| | - Guo-Dong Chang
- Department of Arrhythmia, Shangqiu First People’s Hospital, Shangqiu 476100, Henan Province, China
| | - Xue-Meng Liu
- Department of Arrhythmia, Shangqiu First People’s Hospital, Shangqiu 476100, Henan Province, China
| | - Hui Gao
- Department of Arrhythmia, Shangqiu First People’s Hospital, Shangqiu 476100, Henan Province, China
| | - Xiu-Dan Xu
- Department of Arrhythmia, Shangqiu First People’s Hospital, Shangqiu 476100, Henan Province, China
| | - Su-Ying Lv
- Department of Arrhythmia, Shangqiu First People’s Hospital, Shangqiu 476100, Henan Province, China
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Karakasis P, Theofilis P, Lefkou E, Antoniadis AP, Patoulias D, Korantzopoulos P, Fragakis N. Clonal Hematopoiesis of Indeterminate Potential and Atrial Fibrillation: Insights into Pathophysiology and Clinical Implications. Int J Mol Sci 2025; 26:2739. [PMID: 40141381 DOI: 10.3390/ijms26062739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Revised: 02/28/2025] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a novel risk factor for cardiovascular diseases. CHIP is characterized by the expansion of hematopoietic stem cell clones harboring somatic mutations in genes such as TET2, DNMT3A, and ASXL1, which are implicated in inflammation, atrial remodeling, and hypercoagulability. These mutations foster a pro-inflammatory and pro-thrombotic environment conducive to arrhythmogenesis, thereby linking CHIP to the development and progression of atrial fibrillation (AF). Mechanistic insights indicate that CHIP contributes to atrial fibrosis, disrupts calcium signaling, and exacerbates oxidative stress, all of which heighten susceptibility to AF. Clinical studies, including epidemiological and Mendelian randomization analyses, further support the association between CHIP and an increased risk of both incident and progressive AF, with specific mutations such as TET2 and ASXL1 identified as significant contributors. Additionally, CHIP has been linked to adverse outcomes in AF, including elevated rates of heart failure, thromboembolism, and mortality. Understanding CHIP's role in AF pathophysiology offers opportunities for the development of precision medicine approaches, providing novel avenues for early intervention and targeted AF treatment. This review synthesizes current mechanistic and clinical evidence on the role of CHIP in AF, emphasizes its potential as a biomarker for risk stratification, and explores emerging therapeutic strategies targeting CHIP-associated pathways.
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Affiliation(s)
- Paschalis Karakasis
- Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece
| | - Panagiotis Theofilis
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Eleftheria Lefkou
- Perigenesis, Institute of Obstetric Haematology, 54623 Thessaloniki, Greece
| | - Antonios P Antoniadis
- Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece
| | - Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Faculty of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
| | - Panagiotis Korantzopoulos
- First Department of Cardiology, School of Health Sciences, Faculty of Medicine, University of Ioannina, 45500 Ioannina, Greece
| | - Nikolaos Fragakis
- Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece
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Yang Y, Fan A, Lin H, Wang X, Yang K, Zhang H, Fan G, Li L. Role of macrophages in cardiac arrhythmias: Pathogenesis and therapeutic perspectives. Int Immunopharmacol 2025; 149:114206. [PMID: 39923583 DOI: 10.1016/j.intimp.2025.114206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 01/30/2025] [Indexed: 02/11/2025]
Abstract
The pathophysiology of arrhythmias is complex, involving changes in cardiac contractile and conduction systems, electrical conduction heterogeneity, and structural alterations. Recent studies indicate that cardiac macrophages can induce arrhythmias by interacting with cardiomyocytes or altering tissue composition. Due to the heterogeneity and diversity, macrophages develop different cellular functions during pathological processes. This review identifies various macrophage subpopulations and focuses on their pathological mechanisms in arrhythmogenesis. Furthermore, we explore the interactions of macrophages with other immune cells and summarize the promising approaches for targeting macrophages in arrhythmias treatment. Macrophages directly or indirectly influence arrhythmogenesis through multiple systemic effects. Preclinical studies suggest that modifying macrophages' phenotype or regulating their activity may directly affect cardiac conduction. This review provides a theoretical basis for developing immunotherapies for patients with cardiac arrhythmias.
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Affiliation(s)
- Yakun Yang
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Aodi Fan
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hanqing Lin
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xizheng Wang
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ke Yang
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Haixia Zhang
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guanwei Fan
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
| | - Lan Li
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae for the Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
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Moreno-Loaiza O, Soares VC, de Assumpção Souza M, Vera-Nuñez N, Rodriguez de Yurre Guirao A, da Silva TP, Pozes AB, Perticarrari L, Monteiro E, Albino MC, Silva SB, Dias SSG, Maciel L, Muzi-Filho H, de Oliveira DF, Braga BC, Diniz LP, Cruz MC, Barbosa SR, Castro-Junior AB, Conde L, Cabral-Castro MJ, de Souza OF, Tavares Pinheiro MV, Araújo de Oliveira Junior N, Rezende de Siqueira L, Cosenza RP, Munhoz da Fontoura C, Secco JCP, da Rocha Ferreira J, Silvestre de Sousa A, Albuquerque D, Luiz RR, Nicolau-Neto P, Pretti MA, Boroni M, Bonamino MH, Kasai-Brunswick TH, Mello DB, Gonçalves-Silva T, Ramos IP, Bozza FA, Madeiro JPDV, Pedrosa RC, Carneiro-Ramos MS, da Silva Martinho H, Bozza PT, Mesquita de Souza F, Victor Lucena da Silva G, Cunha TM, Uzelac I, Fenton F, Moll-Bernardes R, Paiva CN, Escobar AL, Medei E. IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression. NATURE CARDIOVASCULAR RESEARCH 2025; 4:312-329. [PMID: 39915330 DOI: 10.1038/s44161-025-00610-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 01/09/2025] [Indexed: 03/19/2025]
Abstract
Atrial fibrillation (AF) is more prevalent in patients with elevated interleukin (IL)-1β levels. Here we show that daily administration of IL-1β for 15 days sensitizes mice to AF, leading to fibrosis, accumulation of β-pleated sheet proteins in the left atrium, and systemic inflammation, resembling the pathophysiological changes observed in patients with AF. IL-1β administration creates a positive feedback loop, dependent on the IL-1 receptor (IL-1R) activity in cardiac resident macrophages. This results in increased caspase-1 maturation in the left atrium and elevated Il1b and Casp1 transcription in atrial macrophages. IL-1β treatment accelerated action potential and Ca2+ restitution in the left atrium, leading to action-potential shortening. This, along with increased caspase-1 maturation and IL-1R signaling, was essential for inducing AF. Lack of IL-1R in macrophages, but not cardiomyocytes, prevented IL-1β-induced AF sensitivity. By depleting recruited macrophages or deleting IL-1R specifically in cardiac resident macrophages, we further demonstrate that IL-1β/IL-1R signaling in these resident macrophages is responsible for increased AF susceptibility. These findings offer insights into the therapeutic potential of targeting IL-1β/IL-1R signaling in patients with AF and emphasize the importance of recognizing different underlying causes in this patient group.
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Affiliation(s)
- Oscar Moreno-Loaiza
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
| | - Vinicius Cardoso Soares
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil
- Program of Immunology and Inflammation, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil
| | - Manuela de Assumpção Souza
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Narendra Vera-Nuñez
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Tatiana Pereira da Silva
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ana Beatriz Pozes
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Larissa Perticarrari
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Evelin Monteiro
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria Clara Albino
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sophia Barros Silva
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Suelen Silva Gomes Dias
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil
| | - Leonardo Maciel
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Humberto Muzi-Filho
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Dahienne Ferreira de Oliveira
- Institute of Medical Biochemistry Leopoldo de Meis, Rio de Janeiro, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Bruno Cabral Braga
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Luan Pereira Diniz
- Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mario Costa Cruz
- Centro de Facilidades e Apoio à Pesquisa (CEFAP), Universidade de São Paulo (USP), São Paulo, Brazil
| | | | | | - Luciana Conde
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mauro Jorge Cabral-Castro
- Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Pathology Department, Fluminense Federal University, Niterói, Brazil
| | | | | | | | | | | | | | | | | | | | | | - Ronir Raggio Luiz
- Institute for Studies in Public Health-IESC, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Clementino Fraga University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Pedro Nicolau-Neto
- Molecular Carcinogenesis Program, Research Coordination, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil
| | - Marco Antonio Pretti
- Cell and Gene Therapy Program, Research Coordination, National Cancer Institute (INCA), Rio de Janeiro, Brazil
| | - Mariana Boroni
- Laboratory of Bioinformatics and Computational Biology, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil
| | - Martin Hernán Bonamino
- Molecular Carcinogenesis Program, Research Coordination, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil
- Vice-Presidency of Research and Biological Collections (VPPCB), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
| | - Tais Hanae Kasai-Brunswick
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Debora Bastos Mello
- National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Triciana Gonçalves-Silva
- National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Isalira Peroba Ramos
- National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fernando A Bozza
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil
- Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil
| | | | - Roberto Coury Pedrosa
- Clementino Fraga University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Patrícia T Bozza
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- Center for Research, Innovation and Surveillance in COVID-19 and Heath Emergencies, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil
| | - Fernanda Mesquita de Souza
- Center of Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, Ribeirão Preto, Brazil
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Gabriel Victor Lucena da Silva
- Center for Natural and Human Sciences, Federal University of ABC, Santo André, Brazil
- Center of Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, Ribeirão Preto, Brazil
| | - Thiago M Cunha
- Center of Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, Ribeirão Preto, Brazil
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil
| | - Ilija Uzelac
- Virginia Commonwealth University, Richmond, VA, USA
| | | | | | - Claudia N Paiva
- Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ariel L Escobar
- Department of Bioengineering, School of Engineering, University of California, Merced, CA, USA
| | - Emiliano Medei
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
- D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
- National Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
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Ren Y, Du X, Li M, Chen L, Liu J, Wu Y, Lu Y. CMR assessment of epicardial edipose tissue in relation to myocardial inflammation and fibrosis in patients with new-onset atrial arrhythmias after STEMI. BMC Cardiovasc Disord 2025; 25:34. [PMID: 39833688 PMCID: PMC11748530 DOI: 10.1186/s12872-025-04486-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 01/08/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Previous studies have shown that epicardial edipose tissue(EAT) appears to be associated with myocardial inflammation and fibrosis, but this is not clear in patients with new-onset atrial arrhythmias after STEMI. The present study focused on using CMR to assess the association of epicardial fat with myocardial inflammation and fibrosis and its predictive value in patients with new-onset atrial arrhythmias after STEMI. METHODS This was a single-centre, retrospective study. We consecutively selected patients who completed CMR during their hospitalisation for PCI after STEMI from May 2019-January 2023, and then underwent regular follow-up, grouped by the presence or absence of new atrial arrhythmias, and enrolled patients were divided into atrial arrhythmia and non-atrial arrhythmia groups. RESULTS In the atrial arrhythmia group, age, heart rate, Peak hs-TnT, PeakNT-proBNP, EATV, LAES, LAED, T1 native, T1*, ECV, and T2 were higher than those in the non-atrial arrhythmia group, and LVEF was lower than those in the non-atrial arrhythmia group. EATV showed a positive and significant correlation with T1native, T1*, ECV, and T2. (T1 native: r = 0.476,p < 0.001; ECV: r = 0.529,p < 0.001; T1*: r = 0.467,p < 0.001; T2: r = 0.538,p < 0.001). Multifactorial logistic regression analysis showed age, LVEF, EATV, T1*,ECV, T2 as independent risk factors for atrial arrhythmia. (p < 0.05) ROC analysis showed that the AUC for age was 0.568; AUC for LVEF was 0.656; AUC for EATV was 0.768; AUC for ECV was 0.705; AUC for T1* was 0.612; and AUC for T2 was 0.772. CONCLUSION In patients with STEMI, EAT is associated with myocardial inflammation, fibrosis. Age, LVEF, EATV, T1*,ECV, T2 are independent risk factors for new onset atrial arrhythmias and have good predictive value.
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Affiliation(s)
- Yanfei Ren
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99#, Huaihai West Road, Xuzhou, 221002, China
| | - Xinjia Du
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99#, Huaihai West Road, Xuzhou, 221002, China
| | - Maochen Li
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99#, Huaihai West Road, Xuzhou, 221002, China
| | - Lei Chen
- Department of Cardiology, Tongji University School of Medicine, Shanghai Tenth People's Hospital, Shanghai, China
| | - Jiahua Liu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99#, Huaihai West Road, Xuzhou, 221002, China
| | - Yixuan Wu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99#, Huaihai West Road, Xuzhou, 221002, China
| | - Yuan Lu
- Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99#, Huaihai West Road, Xuzhou, 221002, China.
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Li L, Wu L, Hu Z, Liu L, Zhou L, Zhang Z, Zhao M, Xiong Y, Zhang Z, Zheng L, Ding L, Yao Y. Association between autoimmune diseases and all-cause mortality in patients with cardiac arrhythmia. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2024:S1885-5857(24)00369-4. [PMID: 39746441 DOI: 10.1016/j.rec.2024.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 12/05/2024] [Indexed: 01/04/2025]
Abstract
INTRODUCTION AND OBJECTIVES Autoimmune diseases (ADs) are associated with an increased risk of developing certain cardiac arrhythmias. However, their prognostic effect in patients with cardiac arrhythmias has not been comprehensively investigated. We aimed to assess the association between ADs and prognosis in this population. METHODS Based on a large retrospective observational cohort, this study included patients with various cardiac arrhythmias, including atrial fibrillation/atrial flutter (AF/AFl), ventricular tachycardia/ventricular fibrillation (VT/VF), and bradyarrhythmias. ADs were considered an exposure factor. The endpoint was all-cause mortality. Cox proportional hazards regression analyses were performed to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) to quantify associations. Propensity score matching was used to mitigate potential confounding bias. RESULTS The analysis included 14 225 patients (mean age, 73.9±12.5 years, 59.2% women), of whom 4552 (32.0%) died within 1 year of discharge. After adjustment for various covariates, patients with ADs showed a higher risk of mortality in AF/AFl (HR, 1.23; 95%CI, 1.1-1.33; P<.001) and VT/VF (HR, 1.28; 95%CI, 1.02-1.60, P=.032). For bradyarrhythmias, although a potential association was observed, the trend did not reach statistical significance (HR, 1.20; 95%CI, 0.93-1.56; P=.168). The association persisted among multiple sensitivity analyses and remained consistent after adjustment for a wide range of covariates. CONCLUSIONS ADs were significantly associated with an increased risk of all-cause mortality in patients with cardiac arrhythmias, particularly in those with AF/AFl and VT/VF.
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Affiliation(s)
- Le Li
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Lingmin Wu
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Zhicheng Hu
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Limin Liu
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Likun Zhou
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Zhuxin Zhang
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Minghao Zhao
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yulong Xiong
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Zhenhao Zhang
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Lihui Zheng
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Ligang Ding
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yan Yao
- Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
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Xu Q, Zhang X, Hao M, Dang X, Xu Q, Cyganek L, Akin I, Tang D, Liao B, Zhou X, Lan H. Esophageal Cancer-Related Gene-4 Contributes to Lipopolysaccharide-Induced Ion Channel Dysfunction in hiPSC-Derived Cardiomyocytes. J Inflamm Res 2024; 17:10183-10197. [PMID: 39649417 PMCID: PMC11624686 DOI: 10.2147/jir.s470828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 11/22/2024] [Indexed: 12/10/2024] Open
Abstract
Background and Purpose Esophageal cancer-related gene-4 (ECRG4) participate in inflammation process and can interact with the innate immunity complex TLR4-MD2-CD14 on human granulocytes. In addition, ECRG4 participate in modulation of ion channel function and electrical activity of cardiomyocytes. However, the exact mechanism is unknown. This study aimed to test our hypothesis that ECRG4 contributes to inflammation-induced ion channel dysfunctions in cardiomyocytes. Methods Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from three donors were treated with lipopolysaccharide (LPS) to establish an endotoxin-induced inflammatory model. Immunostaining, real-time PCR, and patch-clamp techniques were used for the study. Results ECRG4 was detected in hiPSC-CMs at different differentiation time. LPS treatment increased ECRG4 expression in hiPSC-CMs. Knockdown of ECRG4 decreased the expression level of Toll-Like-Receptor 4 (TLR4, a LPS receptor) and its associated genes and inflammatory cytokines. Furthermore, ECRG4 knockdown shortened the action potential duration (APD) and intercepted LPS-induced APD prolongation by enhancing ISK (small conductance calcium-activated K channel current) and attenuating INCX (Na/Ca exchanger current). Overexpression of ECRG4 mimicked LPS effects on ISK and INCX, which could be prevented by NFκB signaling blockers. Conclusion This study demonstrated that LPS effects on cardiac ion channel function were mediated by the upregulation of ECRG4, which affects NFκB signaling. Our findings support the roles of ECRG4 in inflammatory responses and the ion channel dysfunctions induced by LPS challenge.
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Affiliation(s)
- Qiang Xu
- School of Basic Medical Science, Southwest Medical University, Luzhou, People’s Republic of China
- First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany
| | - Xiangjie Zhang
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Department of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Maolin Hao
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Department of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Xitong Dang
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Department of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - QianQian Xu
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Department of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Lukas Cyganek
- Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site, Göttingen, Germany
| | - Ibrahim Akin
- First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg, Mannheim, Germany
| | - Dan Tang
- The First People’s Hospital of Longquanyi District, Chengdu/West China Longquan Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Bin Liao
- Department of Cardiac Macrovascular Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China
| | - Xiaobo Zhou
- First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Department of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China
- DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg, Mannheim, Germany
| | - Huan Lan
- Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Department of Cardiology, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China
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Karanikola AE, Soulaidopoulos S, Leontsinis I, Dri E, Sagris M, Kordalis A, Aznaouridis K, Tsiachris D, Tsioufis K. Arrhythmias Following Patent Foramen Ovale Closure: An Unsolved Enigma. Life (Basel) 2024; 14:1590. [PMID: 39768297 PMCID: PMC11678317 DOI: 10.3390/life14121590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 11/18/2024] [Accepted: 11/22/2024] [Indexed: 01/11/2025] Open
Abstract
Patent foramen ovale (PFO) closure has proven to be an effective method of reducing the risk of recurrent stroke in patients with embolic stroke of unknown origin (ESUS). One of the most recognized post-procedural complications is the de novo occurrence of supraventricular arrhythmias, mainly atrial fibrillation, in the first three months following PFO closure. Earlier studies reported the incidence to be around 3.4-7%; however, this percentage has risen in recent studies up to 21%. The pathogenesis behind this type of arrhythmia is complex and not clearly understood, although it seems that direct effects of the device on the atria, as well as an inflammatory response, are the two most prevalent mechanisms. Management of this complication might be challenging given the heterogenicity of patient characteristics, so an individualized approach is most wisely followed. This review aims to present the current data on the incidence, pathogenesis and therapeutic strategies behind this rather common concern in an era of increasing transcatheter interventions for PFO.
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Affiliation(s)
| | - Stergios Soulaidopoulos
- First Department of Cardiology, Hippokration Hospital, Athens Medical School, National and Kapodistrian University of Athens, Vas. Sofias 114, 11527 Athens, Greece (D.T.)
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9
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Bogert NV, Therre M, Din S, Furkel J, Zhou X, El-Battrawy I, Heineke J, Schweizer PA, Akin I, Katus HA, Frey N, Leuschner F, Konstandin MH. Macrophages enhance sodium channel expression in cardiomyocytes. Basic Res Cardiol 2024; 119:1063-1073. [PMID: 39382673 PMCID: PMC11628573 DOI: 10.1007/s00395-024-01084-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 09/22/2024] [Accepted: 09/29/2024] [Indexed: 10/10/2024]
Abstract
Cardiac macrophages facilitate electrical conduction through the atrioventricular-node (AV) in mice. A possible role for cardiomyocyte-macrophage coupling on the effect of antiarrhythmic therapy has not been investigated yet. Holter monitoring was conducted in LysMCrexCsf1rLsL-DTR mice (MMDTR) under baseline conditions and after an elctrophysiological stress test by flecainide. In vivo effects were recapitulated in vitro by patch-clamp experiments. The underlying mechanism was characterized by expression and localization analysis of connexin43 (Cx43) and voltage-gated-sodium-channel-5 (Nav1.5). ECG monitoring in MMDTR mice did not show any significant conduction abnormalities but a significantly attenuated flecainide-induced extension of RR- and PP-intervals. Patch-clamp analysis revealed that the application of flecainide to neonatal rat ventricular cardiomyocytes (CMs) changed their resting-membrane-potential (RMP) to more negative potentials and decreased action-potential-duration (APD50). Coupling of macrophages to CMs significantly enhances the effects of flecainide, with a further reduction of the RMP and APD50, mediated by an upregulation of Cx43 and Nav1.5 surface expression. Macrophage depletion in mice does not correlate with cardiac electric conduction delay. Cardiac macrophages amplify the effects of flecainide on electrophysiological properties of cardiomyocytes in vivo and in vitro. Mechanistically, formation of macrophage-cardiomyocyte cell-cell-contacts via Cx43 facilitates the recruitment of Nav1.5 to the cell membrane increasing flecainide effects.
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Affiliation(s)
- N V Bogert
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - M Therre
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - S Din
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - J Furkel
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - X Zhou
- Department of Cardiology, University Medical Centre Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - I El-Battrawy
- Department of Cardiology, BG Universitätsklinikum Bergmannsheil Bochum, Ruhr-University, Bochum, Germany
- Institut Für Forschung Und Lehre (IFL), Molecular and Experimental Cardiology, Ruhr University Bochum, Bochum, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - J Heineke
- Department of Cardiovascular Physiology, European Center for Angioscience, Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - P A Schweizer
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - I Akin
- Department of Cardiology, University Medical Centre Mannheim, Ruprecht-Karls-University Heidelberg, Mannheim, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - H A Katus
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - N Frey
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - F Leuschner
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany
| | - M H Konstandin
- Department of Cardiology, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
- German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg, Mannheim, Germany.
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10
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Nayak TK, Parasania D, Tilley DG. Adrenergic orchestration of immune cell dynamics in response to cardiac stress. J Mol Cell Cardiol 2024; 196:115-124. [PMID: 39303854 DOI: 10.1016/j.yjmcc.2024.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/30/2024] [Accepted: 09/10/2024] [Indexed: 09/22/2024]
Abstract
Immune cells contribute approximately 5-10 % of the heart's total cell population, including several myeloid cell and lymphocyte cell subsets, which, despite their relatively small percentages, play important roles in cardiac homeostasis and remodeling responses to various forms of injury and long-term stress. Pathological cardiac stress activates the sympathetic nervous system (SNS), resulting in the release of the catecholamines epinephrine and norepinephrine either systemically or from sympathetic nerve terminals within various lymphoid organs. Acting at α- or β-adrenergic receptors (αAR, βAR), catecholamines regulate immune cell hematopoiesis, egress and migration in response to stress. Classically, αAR stimulation tends to promote inflammatory responses while βAR stimulation has typically been shown to be immunosuppressive, though the effects can be nuanced depending on the immune cells subtype, the site of regulation and pathophysiological context. Herein, we will discuss several facets of SNS-mediated regulation of immune cells and their response to cardiac stress, including: catecholamine response to cardiovascular stress and action at their receptors, adrenergic regulation of hematopoiesis, immune cell retention and release from the bone marrow, adrenergic regulation of splenic immune cells and their retention, as well as adrenergic regulation of immune cell recruitment to the injured heart, including neutrophils, monocytes and macrophages. A particular focus will be given to βAR-mediated effects on myeloid cells in response to acute or chronic cardiac stress.
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Affiliation(s)
- Tapas K Nayak
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
| | - Dev Parasania
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
| | - Douglas G Tilley
- Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
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11
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Fakuade FE, Grune J, Voigt N. Cardiac arrhythmias: the growing role of autoantibodies in diagnosis and treatment. Eur Heart J 2024; 45:4349-4351. [PMID: 39378151 DOI: 10.1093/eurheartj/ehae648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Affiliation(s)
- Funsho E Fakuade
- Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Germany
- Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), University of Göttingen, Germany
- Department of Thoracic and Cardiovascular Surgery, Georg-August-University Göttingen, Germany
| | - Jana Grune
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Institute of Physiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Niels Voigt
- Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Germany
- Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), University of Göttingen, Germany
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12
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Lyu X, Fang J, Liu D, Wu Q, Li Y, Qin C, Zheng J, Hu N. Near-infrared-triggered plasmonic regulation and cardiomyocyte-based biosensing system for in vitro bradyarrhythmia treatment. Biosens Bioelectron 2024; 262:116554. [PMID: 38971038 DOI: 10.1016/j.bios.2024.116554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 06/28/2024] [Accepted: 07/03/2024] [Indexed: 07/08/2024]
Abstract
Bradyarrhythmia, a life-threatening cardiovascular disease, is an increasing burden for the healthcare system. Currently, surgery, implanted device, and drug are introduced to treat the bradyarrhythmia in clinical practice. However, these conventional therapeutic strategies suffer from the invasive surgery, power supply, or drug side effect, respectively, hence developing the alternative therapeutic strategy is necessarily imperative. Here, a convenient and effective strategy to treat the bradyarrhythmia is proposed using near-infrared-triggered Au nanorod (NR) based plasmonic photothermal effect (PPE). Moreover, electrophysiology of cardiomyocytes is dynamically monitored by the integrated biosensing-regulating system during and after the treatment. Cardiomyocyte-based bradyarrhythmia recover rhythmic for a long time by regulating plasmonic photothermal effect. Furthermore, the regulatory mechanism is qualitatively investigated to verify the significant thermal stimulation in the recovery process. This study establishes a reliable platform for long-term recording and evaluation of mild photothermal therapy for bradyarrhythmia in vitro, offering an efficient and non-invasive strategy for the potential clinical applications.
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Affiliation(s)
- Xuelian Lyu
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 310058, China
| | - Jiaru Fang
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 310058, China
| | - Dong Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, School of Electronics and Information Technology, Sun Yat-sen University, Guangzhou, 510006, China
| | - Qianni Wu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, School of Electronics and Information Technology, Sun Yat-sen University, Guangzhou, 510006, China
| | - Ying Li
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Chunlian Qin
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 310058, China
| | - Jilin Zheng
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 310058, China
| | - Ning Hu
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 310058, China; General Surgery Department, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, 310052, China.
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13
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Hu B, Xu D, Shao Y, Nie Z, Liu P, Li J, Zhou L, Wang P, Huang N, Liu J, Lu Y, Wu Z, Wang B, Mei Y, Han M, Li R, Song E. Ultrathin crystalline silicon-based omnidirectional strain gauges for implantable/wearable characterization of soft tissue biomechanics. SCIENCE ADVANCES 2024; 10:eadp8804. [PMID: 39383239 PMCID: PMC11463283 DOI: 10.1126/sciadv.adp8804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 09/05/2024] [Indexed: 10/11/2024]
Abstract
Monitoring soft-tissue biomechanics is of interest in biomedical research and clinical treatment of diseases. An important focus is biointegrated strain gauges that track time-dependent mechanics of targeted tissues with deforming surfaces over multidirections. Existing methods provide limited gauge factors, tailored for sensing within specific directions under quasi-static conditions. We present development and applicability of implantable/wearable strain gauges that integrate multiple ultrathin monocrystalline silicon-based sensors aligned with different directions, in stretchable formats for dynamically monitoring direction angle-sensitive strain. We experimentally and computationally establish operational principles, with theoretical systems that enable determination of intensities and direction of applied strains at an omnidirectional scale. Wearable evaluations range from cardiac pulse to intraocular pressure monitoring of eyeballs. The device can evaluate cardiac disorders of myocardial infarction and hypoxia of living rats and locate the pathological orientation associated with infarction, in designs with possibilities as biodegradable implants for stable operation. These findings create clinical significance of the devices for monitoring complex dynamic biomechanics.
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Affiliation(s)
- Bofan Hu
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
| | - Dian Xu
- School of Mechanics and Aerospace Engineering, State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, and International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116024, China
| | - Yuting Shao
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China
| | - Zhongyi Nie
- Department of Biomedical Engineering, College of Future technology, Peking University, Beijing 100871, China
| | - Pengchuan Liu
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Jinbao Li
- School of Mechanics and Aerospace Engineering, State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, and International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116024, China
| | - Lianjie Zhou
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Pei Wang
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200003, China
| | - Ningge Huang
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Junhan Liu
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Yifei Lu
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Zhongyuan Wu
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Bo Wang
- School of Mechanics and Aerospace Engineering, State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, and International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116024, China
| | - Yongfeng Mei
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- Yiwu Research Institute of Fudan University, Yiwu, Zhejiang 322000, China
| | - Mengdi Han
- Department of Biomedical Engineering, College of Future technology, Peking University, Beijing 100871, China
| | - Rui Li
- School of Mechanics and Aerospace Engineering, State Key Laboratory of Structural Analysis, Optimization and CAE Software for Industrial Equipment, and International Research Center for Computational Mechanics, Dalian University of Technology, Dalian 116024, China
| | - Enming Song
- Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Institute of Optoelectronics, Department of Materials Science, Fudan University, Shanghai, China
- International Institute for Intelligent Nanorobots and Nanosystems, Fudan University, Shanghai 200438, China
- State Key Laboratory of Integrated Chips and Systems, Frontier Institute of Chip and System, Fudan University, Shanghai 200438, China
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14
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Lei Q, Jiang Z, Shao Y, Liu X, Li X. Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation. Front Cardiovasc Med 2024; 11:1453127. [PMID: 39328238 PMCID: PMC11424448 DOI: 10.3389/fcvm.2024.1453127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 08/29/2024] [Indexed: 09/28/2024] Open
Abstract
Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.
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Affiliation(s)
- Qiulian Lei
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Zefei Jiang
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Yu Shao
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xinghong Liu
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiaoping Li
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Department of Cardiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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15
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Hutschalik T, Özgül O, Casini M, Szabó B, Peyronnet R, Bártulos Ó, Argenziano M, Schotten U, Matsa E. Immune response caused by M1 macrophages elicits atrial fibrillation-like phenotypes in coculture model with isogenic hiPSC-derived cardiomyocytes. Stem Cell Res Ther 2024; 15:280. [PMID: 39227896 PMCID: PMC11373469 DOI: 10.1186/s13287-024-03814-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 06/24/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Atrial fibrillation has an estimated prevalence of 1.5-2%, making it the most common cardiac arrhythmia. The processes that cause and sustain the disease are still not completely understood. An association between atrial fibrillation and systemic, as well as local, inflammatory processes has been reported. However, the exact mechanisms underlying this association have not been established. While it is understood that inflammatory macrophages can influence cardiac electrophysiology, a direct, causative relationship to atrial fibrillation has not been described. This study investigated the pro-arrhythmic effects of activated M1 macrophages on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes, to propose a mechanistic link between inflammation and atrial fibrillation. METHODS Two hiPSC lines from healthy individuals were differentiated to atrial cardiomyocytes and M1 macrophages and integrated in an isogenic, pacing-free, atrial fibrillation-like coculture model. Electrophysiology characteristics of cocultures were analysed for beat rate irregularity, electrogram amplitude and conduction velocity using multi electrode arrays. Cocultures were additionally treated using glucocorticoids to suppress M1 inflammation. Bulk RNA sequencing was performed on coculture-isolated atrial cardiomyocytes and compared to meta-analyses of atrial fibrillation patient transcriptomes. RESULTS Multi electrode array recordings revealed M1 to cause irregular beating and reduced electrogram amplitude. Conduction analysis further showed significantly lowered conduction homogeneity in M1 cocultures. Transcriptome sequencing revealed reduced expression of key cardiac genes such as SCN5A, KCNA5, ATP1A1, and GJA5 in the atrial cardiomyocytes. Meta-analysis of atrial fibrillation patient transcriptomes showed high correlation to the in vitro model. Treatment of the coculture with glucocorticoids showed reversal of phenotypes, including reduced beat irregularity, improved conduction, and reversed RNA expression profiles. CONCLUSIONS This study establishes a causal relationship between M1 activation and the development of subsequent atrial arrhythmia, documented as irregularity in spontaneous electrical activation in atrial cardiomyocytes cocultured with activated macrophages. Further, beat rate irregularity could be alleviated using glucocorticoids. Overall, these results point at macrophage-mediated inflammation as a potential AF induction mechanism and offer new targets for therapeutic development. The findings strongly support the relevance of the proposed hiPSC-derived coculture model and present it as a first of its kind disease model.
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Affiliation(s)
- Thomas Hutschalik
- Ncardia Services B.V, J.H. Oortweg 21, 2333 CH, Leiden, The Netherlands
- Dept. of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands
| | - Ozan Özgül
- Dept. of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands
| | - Marilù Casini
- Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, 46026, Valencia, Spain
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen and Faculty of Medicine, Freiburg im Breisgau, 79110, Germany
| | - Brigitta Szabó
- Ncardia Services B.V, J.H. Oortweg 21, 2333 CH, Leiden, The Netherlands
| | - Rémi Peyronnet
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen and Faculty of Medicine, Freiburg im Breisgau, 79110, Germany
| | - Óscar Bártulos
- Ncardia Services B.V, J.H. Oortweg 21, 2333 CH, Leiden, The Netherlands
| | | | - Ulrich Schotten
- Dept. of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands
- Dept. of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Elena Matsa
- Ncardia Services B.V, J.H. Oortweg 21, 2333 CH, Leiden, The Netherlands.
- , Rue Edouard Belin 2, 1435, CellisticMont-Saint-Guibert, Belgium.
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
- National Institute for Bioprocessing Research and Training, Dublin, Ireland.
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16
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Liao Y, Zhu L. At the heart of inflammation: Unravelling cardiac resident macrophage biology. J Cell Mol Med 2024; 28:e70050. [PMID: 39223947 PMCID: PMC11369210 DOI: 10.1111/jcmm.70050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 08/13/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024] Open
Abstract
Cardiovascular disease remains one of the leading causes of death globally. Recent advancements in sequencing technologies have led to the identification of a unique population of macrophages within the heart, termed cardiac resident macrophages (CRMs), which exhibit self-renewal capabilities and play crucial roles in regulating cardiac homeostasis, inflammation, as well as injury and repair processes. This literature review aims to elucidate the origin and phenotypic characteristics of CRMs, comprehensively outline their contributions to cardiac homeostasis and further summarize their functional roles and molecular mechanisms implicated in the onset and progression of cardiovascular diseases. These insights are poised to pave the way for novel therapeutic strategies centred on targeted interventions based on the distinctive properties of resident macrophages.
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Affiliation(s)
- Yingnan Liao
- Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduChina
- Research Unit for Blindness Prevention, Chinese Academy of Medical Sciences (2019RU026)Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduSichuanChina
| | - Liyuan Zhu
- Center of Clinical Pharmacology, The Second Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
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17
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Lu D, Fan X. Insights into the prospects of nanobiomaterials in the treatment of cardiac arrhythmia. J Nanobiotechnology 2024; 22:523. [PMID: 39215361 PMCID: PMC11363662 DOI: 10.1186/s12951-024-02805-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024] Open
Abstract
Cardiac arrhythmia, a disorder of abnormal electrical activity of the heart that disturbs the rhythm of the heart, thereby affecting its normal function, is one of the leading causes of death from heart disease worldwide and causes millions of deaths each year. Currently, treatments for arrhythmia include drug therapy, radiofrequency ablation, cardiovascular implantable electronic devices (CIEDs), including pacemakers, defibrillators, and cardiac resynchronization therapy (CRT). However, these traditional treatments have several limitations, such as the side effects of medication, the risks of device implantation, and the complications of invasive surgery. Nanotechnology and nanomaterials provide safer, effective and crucial treatments to improve the quality of life of patients with cardiac arrhythmia. The large specific surface area, controlled physical and chemical properties, and good biocompatibility of nanobiomaterials make them promising for a wide range of applications, such as cardiovascular drug delivery, tissue engineering, and the diagnosis and therapeutic treatment of diseases. However, issues related to the genotoxicity, cytotoxicity and immunogenicity of nanomaterials remain and require careful consideration. In this review, we first provide a brief overview of cardiac electrophysiology, arrhythmia and current treatments for arrhythmia and discuss the potential applications of nanobiomaterials before focusing on the promising applications of nanobiomaterials in drug delivery and cardiac tissue repair. An in-depth study of the application of nanobiomaterials is expected to provide safer and more effective therapeutic options for patients with cardiac arrhythmia, thereby improving their quality of life.
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Affiliation(s)
- Dingkun Lu
- Cardiac Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohan Fan
- Cardiac Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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18
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Zhao H, Li M, Wu D, Chen S, Zhu C, Lan Y, Liu H, Wu Y, Wu S. Physical Activity Modifies the Risk of Incident Cardiac Conduction Disorders Upon Inflammation: A Population-Based Cohort Study. J Am Heart Assoc 2024; 13:e034754. [PMID: 39158550 DOI: 10.1161/jaha.124.034754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 07/24/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND Emerging evidence suggests a central role for inflammation in cardiac conduction disorder (CCD). It is unknown whether habitual physical activity could modulate the inflammation-associated risks of incident CCD in the general population. METHODS AND RESULTS This population-based cohort was derived from the China Kailuan study, including a total of 97 192 participants without prior CCD. The end points included incident CCD and its subcategories (atrioventricular block and bundle-branch block). Systemic inflammation was indicated by the monocyte-to-lymphocyte ratio (MLR). Over a median 10.91-year follow-up, 3747 cases of CCD occurred, with 1062 cases of atrioventricular block and 2697 cases of bundle-branch block. An overall linear dose-dependent relationship was observed between MLR and each study end point (all P-nonlinearity≥0.05). Both higher MLR and physical inactivity were significantly associated with higher risks of conduction block. The MLR-associated risks of developing study end points were higher in the physically inactive individuals than in those being physically active, with significant interactions between MLR levels and physical activity for developing CCD (P-interaction=0.07) and bundle-branch block (P-interaction<0.05) found. Compared with those in MLR quartile 2 and being physically active, those in the highest MLR quartile and being physically inactive had significantly higher risks for all study end points (1.42 [95% CI, 1.24-1.63], 1.62 [95% CI, 1.25-2.10], and 1.33 [95% CI, 1.13-1.56], respectively, for incident CCD, atrioventricular block, and bundle-branch block). CONCLUSIONS MLR should be a biomarker for the risk assessment of incident CCD. Adherence to habitual physical activity is favorable for reducing the MLR-associated risks of CCD.
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Affiliation(s)
- Haiyan Zhao
- Department of Cardiology Kailuan General Hospital Tangshan China
| | - Man Li
- Graduate School North China University of Science and Technology Tangshan China
| | - Dan Wu
- Department of Pediatrics Second Affiliated Hospital of Shantou University Medical College Shantou Guangdong China
- Centre for Precision Health Edith Cowan University School of Medical and Health Sciences Joondalup WA USA
| | - Shuohua Chen
- Department of Cardiology Kailuan General Hospital Tangshan China
| | - Chenrui Zhu
- Department of Cardiology Kailuan General Hospital Tangshan China
| | - Yulong Lan
- Centre for Precision Health Edith Cowan University School of Medical and Health Sciences Joondalup WA USA
- Department of Cardiology Second Affiliated Hospital of Shantou University Medical College Shantou Guangdong China
| | - Hongmin Liu
- Department of Cardiology Kailuan General Hospital Tangshan China
| | - Yuntao Wu
- Department of Cardiology Kailuan General Hospital Tangshan China
| | - Shouling Wu
- Department of Cardiology Kailuan General Hospital Tangshan China
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19
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Fan A, Liu G, Wu X. Nanosecond pulse electric field treatment initiates mitochondrial apoptosis pathway by inducing mitochondrial morphological changes in myocardial cells. J Interv Card Electrophysiol 2024:10.1007/s10840-024-01828-5. [PMID: 39093488 DOI: 10.1007/s10840-024-01828-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 05/09/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND As an emerging myocardial ablation technique, the mechanism of nanosecond pulse electric field (nsPEF) ablation is currently less studied. Mitochondria are one of the important membrane structure organelles in cells, participating in numerous life activities within the cell. This study aimed to explore the morphological changes of mitochondria in living cells following nsPEF treatment. METHODS Myocardial cells were treated with a self-made solid-state LTD high-voltage nanosecond pulse generator with a pulse width of 100 ns for 80 times. The changes in mitochondrial membrane potential and cell apoptosis in rat myocardial cells after nsPEFs were investigated using JC-1 assay kit, apoptosis double staining assay kit, and mitochondrial fluorescence probe. RESULTS The results showed that after nsPEF treatment, the mitochondrial membrane potential decreased, apoptosis increased, and the average mitochondrial area decreased from 0.48 µm2 in live myocardial cells to 0.16 µm2. The average circumference ranges from 3.17 µm dropped to 1.60 µm. The shape factor decreased from 1.92 to 1.41. The aspect ratio has decreased from 2.16 to 1.59. nsPEF treatment induces changes in the morphology of myocardial cell mitochondria. CONCLUSIONS Based on the results of mitochondrial membrane potential and apoptosis, it can be inferred that under this equipment and parameter conditions, nsPEF treatment first causes changes in mitochondrial morphology, and then initiates the mitochondrial apoptosis pathway, which may provide experimental basis for investigating the potential mechanism of nsPEF ablation of myocardial cells.
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Affiliation(s)
- Aqing Fan
- University of Science and Technology of China, Hefei, 230000, China
| | - Gengliang Liu
- University of Science and Technology of China, Hefei, 230000, China
| | - Xiaodong Wu
- Suzhou Institute of Biomedical Engineering Technology, Chinese Academy of Sciences, No. 88 Keling Road, Huqiu District, Suzhou City, 215163, Jiangsu Province, China.
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20
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Ma Z, Chen Q, Liu Z, Li X, Zhang H, Feng X. Genetically predicted inflammatory proteins and the risk of atrial fibrillation: a bidirectional Mendelian randomization study. Front Cardiovasc Med 2024; 11:1375750. [PMID: 38988665 PMCID: PMC11234858 DOI: 10.3389/fcvm.2024.1375750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 05/28/2024] [Indexed: 07/12/2024] Open
Abstract
Purpose The causal associations between inflammatory factors and atrial fibrillation (AF) remained unclear. We aimed to investigate whether genetically predicted inflammatory proteins are related to the risk of AF, and vice versa. Methods A bidirectional two-sample Mendelian randomization study was performed. The genetic variation of 91 inflammatory proteins were derived from genome-wide association study (GWAS) data of European ancestry (n = 14,824). Summary statistics for AF were obtained from a published meta-analysis study (n = 1,030,836) and the FinnGen study (n = 261,395). Results Genetically predicted fibroblast growth factor 5 (FGF5) was significantly positively associated with risk of AF [[odds ratio (OR): 1.07; 95% CI: 1.04-1.10; P < 0.01], and CD40l receptor was significantly negatively associated with risk of AF (OR: 0.95; 95% CI: 0.92-0.98; P = 0.02) in the meta-analysis study. In the FinnGen study, similar results were observed in FGF5 (OR: 1.11; 95% CI: 1.06-1.16; P < 0.01) and CD40l receptor (OR: 0.93; 95% CI: 0.89-0.97; P = 0.03) for AF. In the FinnGen study, TNF-beta was significantly positively associated with risk of AF (OR: 1.05; 95% CI: 1.02-1.09; P = 0.03) and leukemia inhibitory factor receptor was significantly negatively associated with risk of AF (OR: 0.86; 95% CI: 0.80-0.91; P = 0.001). The causal effect of AF on inflammatory proteins was not observed. Conclusion Our study suggested that FGF5 and CD40l receptor have a potential causal association with AF, and targeting these factors may help in the treatment of AF.
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Affiliation(s)
| | | | | | | | - Huaming Zhang
- Division of Cardiology, Departments of Internal Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xi Feng
- Division of Cardiology, Departments of Internal Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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21
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Holt M, Lin J, Cicka M, Wong A, Epelman S, Lavine KJ. Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages. Circ Res 2024; 134:1791-1807. [PMID: 38843293 DOI: 10.1161/circresaha.124.323817] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 05/09/2024] [Indexed: 06/11/2024]
Abstract
Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.
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Affiliation(s)
- Megan Holt
- Division of Cardiology, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine (M.H., M.C., K.J.L.)
| | - Julia Lin
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (J.L., A.W., S.E.)
- Department of Immunology, University of Toronto, ON, Canada (J.L., A.W., S.E.)
| | - Markus Cicka
- Division of Cardiology, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine (M.H., M.C., K.J.L.)
| | - Anthony Wong
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (J.L., A.W., S.E.)
- Department of Immunology, University of Toronto, ON, Canada (J.L., A.W., S.E.)
| | - Slava Epelman
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (J.L., A.W., S.E.)
- Ted Rogers Centre for Heart Research, Translational Biology and Engineering Program, Toronto, ON, Canada (S.E.)
- Department of Immunology, University of Toronto, ON, Canada (J.L., A.W., S.E.)
- Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada (S.E.)
| | - Kory J Lavine
- Division of Cardiology, Department of Medicine, Center for Cardiovascular Research, Washington University School of Medicine (M.H., M.C., K.J.L.)
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22
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Zong H, Hu Z, Li W, Wang M, Zhou Q, Li X, Liu H. Electronic cigarettes and cardiovascular disease: epidemiological and biological links. Pflugers Arch 2024; 476:875-888. [PMID: 38376568 PMCID: PMC11139732 DOI: 10.1007/s00424-024-02925-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/08/2024] [Accepted: 02/09/2024] [Indexed: 02/21/2024]
Abstract
Electronic cigarettes (e-cigarettes), as alternative nicotine delivery methods, has rapidly increased among youth and adults in recent years. However, cardiovascular safety is an important consideration regarding e-cigarettes usage. e-cigarette emissions, including nicotine, propylene glycol, flavorings, nitrosamine, and metals, might have adverse effects on cardiovascular health. A large body of epidemiological evidence has indicated that e-cigarettes are considered an independent risk factor for increased rates of cardiovascular disease occurrence and death. The incidence and mortality of various types of cardiovascular disease, such as cardiac arrhythmia, hypertension, acute coronary syndromes, and heart failure, have a modest growth in vapers (users of e-cigarettes). Although the underlying biological mechanisms have not been fully understood, studies have validated that oxidative stress, inflammation, endothelial dysfunction, atherosclerosis, hemodynamic effects, and platelet function play important roles in which e-cigarettes work in the human body. This minireview consolidates and discusses the epidemiological and biological links between e-cigarettes and various types of cardiovascular disease.
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Affiliation(s)
- Huiqi Zong
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Zhekai Hu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, 100053, China
| | - Weina Li
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Xicheng District, Beijing, 100053, China
| | - Mina Wang
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Qi Zhou
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China
| | - Xiang Li
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
| | - Hongxu Liu
- Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China.
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Mesquita T, Cingolani E. Targeting arrhythmogenic macrophages: lessons learned from arrhythmogenic cardiomyopathy. J Clin Invest 2024; 134:e180482. [PMID: 38747296 PMCID: PMC11093592 DOI: 10.1172/jci180482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2024] Open
Abstract
Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac condition characterized by cardiac remodeling and life-threatening ventricular arrhythmias. In this issue of the JCI, Chelko, Penna, and colleagues mechanistically addressed the intricate contribution of immune-mediated injury in ACM pathogenesis. Inhibition of nuclear factor κ-B (NF-κB) and infiltration of monocyte-derived macrophages expressing C-C motif chemokine receptor-2 (CCR2) alleviated the phenotypic ACM features (i.e., fibrofatty replacement, contractile dysfunction, and ventricular arrhythmias) in desmoglein 2-mutant (Dsg2mut/mut) mice. These findings pave the way for efficacious and targetable immune therapy for patients with ACM.
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24
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Wang M, Li C, Liu Y, Jin Y, Yu Y, Tan X, Zhang C. The effect of macrophages and their exosomes in ischemic heart disease. Front Immunol 2024; 15:1402468. [PMID: 38799471 PMCID: PMC11116575 DOI: 10.3389/fimmu.2024.1402468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 04/29/2024] [Indexed: 05/29/2024] Open
Abstract
Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.
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Affiliation(s)
- Minrui Wang
- Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China
| | - Chunhong Li
- Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Yuchang Liu
- Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Yuanyuan Jin
- The Key Laboratory of Medical Electrophysiology of the Ministry of Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Yang Yu
- The Key Laboratory of Medical Electrophysiology of the Ministry of Education, Southwest Medical University, Luzhou, Sichuan, China
| | - Xiaoqiu Tan
- Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, China
- The Key Laboratory of Medical Electrophysiology of the Ministry of Education, Southwest Medical University, Luzhou, Sichuan, China
- Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Chunxiang Zhang
- The Key Laboratory of Medical Electrophysiology of the Ministry of Education, Southwest Medical University, Luzhou, Sichuan, China
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Patel P, Patel SH, Siddegowda A, Potini BR, Miriyala V, Patel D, Singh N. Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. Cureus 2024; 16:e61374. [PMID: 38947715 PMCID: PMC11214541 DOI: 10.7759/cureus.61374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/29/2024] [Indexed: 07/02/2024] Open
Abstract
Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.
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Affiliation(s)
- Priyansh Patel
- Department of Cardiovascular Medicine, University of Miami Miller School of Medicine, Miami, USA
| | - Saloni H Patel
- Department of Internal Medicine, Smt. Nathiba Hargovandas Lakhmichand Municipal Medical College, Ahmedabad, IND
| | - Akshaya Siddegowda
- Department of Internal Medicine, Jagadguru Sri Shivarathreeshwara Medical College, Mysore, IND
| | | | - Varsha Miriyala
- Department of Internal Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, IND
| | - Diya Patel
- Department of Internal Medicine, Gujarat Medical Education and Research Society, Sola, Ahmedabad, IND
| | - Navpreet Singh
- Department of Internal Medicine, Gian Sagar Medical College and Hospital, Patiala, IND
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Paquette SE, Oduor CI, Gaulke A, Stefan S, Bronk P, Dafonseca V, Barulin N, Lee C, Carley R, Morrison AR, Choi BR, Bailey JA, Plavicki JS. Loss of developmentally derived Irf8+ macrophages promotes hyperinnervation and arrhythmia in the adult zebrafish heart. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.17.589909. [PMID: 38659956 PMCID: PMC11042273 DOI: 10.1101/2024.04.17.589909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
Recent developments in cardiac macrophage biology have broadened our understanding of the critical functions of macrophages in the heart. As a result, there is further interest in understanding the independent contributions of distinct subsets of macrophage to cardiac development and function. Here, we demonstrate that genetic loss of interferon regulatory factor 8 (Irf8)-positive embryonic-derived macrophages significantly disrupts cardiac conduction, chamber function, and innervation in adult zebrafish. At 4 months post-fertilization (mpf), homozygous irf8st96/st96 mutants have significantly shortened atrial action potential duration and significant differential expression of genes involved in cardiac contraction. Functional in vivo assessments via electro- and echocardiograms at 12 mpf reveal that irf8 mutants are arrhythmogenic and exhibit diastolic dysfunction and ventricular stiffening. To identify the molecular drivers of the functional disturbances in irf8 null zebrafish, we perform single cell RNA sequencing and immunohistochemistry, which reveal increased leukocyte infiltration, epicardial activation, mesenchymal gene expression, and fibrosis. Irf8 null hearts are also hyperinnervated and have aberrant axonal patterning, a phenotype not previously assessed in the context of cardiac macrophage loss. Gene ontology analysis supports a novel role for activated epicardial-derived cells (EPDCs) in promoting neurogenesis and neuronal remodeling in vivo. Together, these data uncover significant cardiac abnormalities following embryonic macrophage loss and expand our knowledge of critical macrophage functions in heart physiology and governing homeostatic heart health.
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Affiliation(s)
- Shannon E. Paquette
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Cliff I. Oduor
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Amy Gaulke
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Sabina Stefan
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA
| | - Peter Bronk
- Cardiovascular Research Center, Brown University Warren Alpert Medical School, Providence, RI, 02912, USA
| | - Vanny Dafonseca
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Nikolai Barulin
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Cadence Lee
- Vascular Research Laboratory, Providence VA Medical Center, Providence, RI, 02908, USA
- Ocean State Research Institute, Inc., Providence, RI, 02908, USA
| | - Rachel Carley
- Vascular Research Laboratory, Providence VA Medical Center, Providence, RI, 02908, USA
- Ocean State Research Institute, Inc., Providence, RI, 02908, USA
| | - Alan R. Morrison
- Vascular Research Laboratory, Providence VA Medical Center, Providence, RI, 02908, USA
- Ocean State Research Institute, Inc., Providence, RI, 02908, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, RI, 02903, USA
| | - Bum-Rak Choi
- Cardiovascular Research Center, Brown University Warren Alpert Medical School, Providence, RI, 02912, USA
| | - Jeffrey A. Bailey
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Jessica S. Plavicki
- Department of Pathology & Laboratory Medicine, Brown University, Providence, RI, 02912, USA
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Mesquita T, Lin YN, Chen S, Lee Y, Miguel-dos-Santos R, Atici AE, Fishbein MC, Rivas MN, Arditi M, Cingolani E. Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease. Arterioscler Thromb Vasc Biol 2024; 44:e117-e130. [PMID: 38385289 PMCID: PMC10978283 DOI: 10.1161/atvbaha.123.320382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/09/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. METHODS Lactobacillus casei cell wall extract-induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. RESULTS KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1β and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract-injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. CONCLUSIONS Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract-induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.
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Affiliation(s)
- Thassio Mesquita
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Yen-Nien Lin
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Shuang Chen
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, California, USA
- Infectious and Immunologic Diseases Research Center (IIDRC) and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Youngho Lee
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, California, USA
- Infectious and Immunologic Diseases Research Center (IIDRC) and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | | | - Asli E. Atici
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, California, USA
- Infectious and Immunologic Diseases Research Center (IIDRC) and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Michael C. Fishbein
- Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Magali Noval Rivas
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, California, USA
- Infectious and Immunologic Diseases Research Center (IIDRC) and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Moshe Arditi
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, California, USA
- Infectious and Immunologic Diseases Research Center (IIDRC) and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Eugenio Cingolani
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
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Pang Y, Xu Y, Chen Q, Cheng K, Ling Y, Jang J, Ge J, Zhu W. FLRT3 and TGF-β/SMAD4 signalling: Impacts on apoptosis, autophagy and ion channels in supraventricular tachycardia. J Cell Mol Med 2024; 28:e18237. [PMID: 38509727 PMCID: PMC10955158 DOI: 10.1111/jcmm.18237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 01/14/2024] [Accepted: 02/28/2024] [Indexed: 03/22/2024] Open
Abstract
To explore the underlying molecular mechanisms of supraventricular tachycardia (SVT), this study aimed to analyse the complex relationship between FLRT3 and TGF-β/SMAD4 signalling pathway, which affects Na+ and K+ channels in cardiomyocytes. Bioinformatics analysis was performed on 85 SVT samples and 15 healthy controls to screen overlapping genes from the key module and differentially expressed genes (DEGs). Expression profiling of overlapping genes, coupled with Receiver Operating Characteristic (ROC) curve analyses, identified FLRT3 as a hub gene. In vitro studies utilizing Ang II-stimulated H9C2 cardiomyocytes were undertaken to elucidate the consequences of FLRT3 silencing on cardiomyocyte apoptosis and autophagic processes. Utilizing a combination of techniques such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting (WB), flow cytometry, dual-luciferase reporter assays and chromatin immunoprecipitation polymerase chain reaction (ChIP-PCR) assays were conducted to decipher the intricate interactions between FLRT3, the TGF-β/SMAD4 signalling cascade and ion channel gene expression. Six genes (AADAC, DSC3, FLRT3, SYT4, PRR9 and SERTM1) demonstrated reduced expression in SVT samples, each possessing significant clinical diagnostic potential. In H9C2 cardiomyocytes, FLRT3 silencing mitigated Ang II-induced apoptosis and modulated autophagy. With increasing TGF-β concentration, there was a dose-responsive decline in FLRT3 and SCN5A expression, while both KCNIP2 and KCND2 expressions were augmented. Moreover, a direct interaction between FLRT3 and SMAD4 was observed, and inhibition of SMAD4 expression resulted in increased FLRT3 expression. Our results demonstrated that the TGF-β/SMAD4 signalling pathway plays a critical role by regulating FLRT3 expression, with potential implications for ion channel function in SVT.
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Affiliation(s)
- Yang Pang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Ye Xu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Qingxing Chen
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Kuan Cheng
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Yunlong Ling
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Jun Jang
- State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life ScienceFudan UniversityShanghaiChina
| | - Junbo Ge
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Wenqing Zhu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan HospitalFudan UniversityShanghaiChina
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29
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Li Q, Nie J, Cao M, Luo C, Sun C. Association between inflammation markers and all-cause mortality in critical ill patients with atrial fibrillation: Analysis of the Multi-Parameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database. IJC HEART & VASCULATURE 2024; 51:101372. [PMID: 38435383 PMCID: PMC10905960 DOI: 10.1016/j.ijcha.2024.101372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 02/21/2024] [Indexed: 03/05/2024]
Abstract
Background Inflammation is related to cardiovascular disease. Among the many inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) were considered as novel predictors for atherosclerosis outcomes. We aimed to investigate the impact of these inflammatory markers on the prognosis of patients with atrial fibrillation (AF). Methods We obtained data on AF patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. These patients were classified into two groups based on their survival status within 30 days. Then, they were divided into three groups based on the tertile of baseline NLR, PLR, and SII, respectively. We comprehensively explored the relationship between those inflammatory indicators and all-cause mortality in patients with AF by Kaplan-Meier analysis, multivariate Cox regression analysis, receiver operating characteristic (ROC) analyses, restricted cubic spline regression (RCS), and subgroup analysis. Results A total of 4562 patients with AF were included. Statistically significant differences were found between survivor and non-survivor groups for NLR, PLR and SII. Patients in the high tertile of the NLR had a higher mortality rate than those in the low and intermediate tertiles, as did patients in the PLR and the SII. NLR, PLR and SII were independently associated with increased risk of all-cause mortality. RCS showed that the 30-day and 365-day risk of death were linearly associated with increases in NLR, PLR, and SII, respectively. Conclusion NLR, PLR, and SII have the potential to be used as indicators for stratifying the risk of mortality in critically ill patients with AF.
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Affiliation(s)
- Qian Li
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, PR China
| | - Jian Nie
- Department of Senile Diseases, Shaanxi Provincial People’s Hospital, No. 256 Youyi West Road, Xi’an 710068, PR China
| | - Miaomiao Cao
- Department of Radiology, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, PR China
| | - Chaodi Luo
- Department of Peripheral Vascular Diseases, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, PR China
| | - Chaofeng Sun
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, PR China
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30
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Schuermans A, Vlasschaert C, Nauffal V, Cho SMJ, Uddin MM, Nakao T, Niroula A, Klarqvist MDR, Weeks LD, Lin AE, Saadatagah S, Lannery K, Wong M, Hornsby W, Lubitz SA, Ballantyne C, Jaiswal S, Libby P, Ebert BL, Bick AG, Ellinor PT, Natarajan P, Honigberg MC. Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias. Eur Heart J 2024; 45:791-805. [PMID: 37952204 PMCID: PMC10919923 DOI: 10.1093/eurheartj/ehad670] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 09/07/2023] [Accepted: 09/26/2023] [Indexed: 11/14/2023] Open
Abstract
BACKGROUND AND AIMS Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias. METHODS UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested. RESULTS This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR. CONCLUSIONS CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.
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Affiliation(s)
- Art Schuermans
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
| | | | - Victor Nauffal
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - So Mi Jemma Cho
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Md Mesbah Uddin
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
| | - Tetsushi Nakao
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Abhishek Niroula
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Laboratory Medicine, Lund University, Lund, Sweden
| | | | - Lachelle D Weeks
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Amy E Lin
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | | | - Kim Lannery
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
| | - Megan Wong
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
| | - Whitney Hornsby
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
| | - Steven A Lubitz
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Department of Medicine, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
| | | | - Siddhartha Jaiswal
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Peter Libby
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Benjamin L Ebert
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Medicine, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
- Howard Hughes Medical Institute, Boston, MA, USA
| | - Alexander G Bick
- Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Patrick T Ellinor
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Department of Medicine, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
| | - Pradeep Natarajan
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Department of Medicine, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
| | - Michael C Honigberg
- Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, 75 Ames St., Cambridge, MA 02142, USA
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA
- Department of Medicine, Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
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Hegemann N, Barth L, Döring Y, Voigt N, Grune J. Implications for neutrophils in cardiac arrhythmias. Am J Physiol Heart Circ Physiol 2024; 326:H441-H458. [PMID: 38099844 PMCID: PMC11219058 DOI: 10.1152/ajpheart.00590.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 12/08/2023] [Accepted: 12/13/2023] [Indexed: 02/03/2024]
Abstract
Cardiac arrhythmias commonly occur as a result of aberrant electrical impulse formation or conduction in the myocardium. Frequently discussed triggers include underlying heart diseases such as myocardial ischemia, electrolyte imbalances, or genetic anomalies of ion channels involved in the tightly regulated cardiac action potential. Recently, the role of innate immune cells in the onset of arrhythmic events has been highlighted in numerous studies, correlating leukocyte expansion in the myocardium to increased arrhythmic burden. Here, we aim to call attention to the role of neutrophils in the pathogenesis of cardiac arrhythmias and their expansion during myocardial ischemia and infectious disease manifestation. In addition, we will elucidate molecular mechanisms associated with neutrophil activation and discuss their involvement as direct mediators of arrhythmogenicity.
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Affiliation(s)
- Niklas Hegemann
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
| | - Lukas Barth
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
| | - Yannic Döring
- Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg August University Göttingen, Göttingen, Germany
- German Centre for Cardiovascular Research (DZHK), Göttingen, Germany
| | - Niels Voigt
- Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg August University Göttingen, Göttingen, Germany
- German Centre for Cardiovascular Research (DZHK), Göttingen, Germany
- Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany
| | - Jana Grune
- Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Berlin, Germany
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Centre for Cardiovascular Research (DZHK), Berlin, Germany
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Khan SU, Huang Y, Ali H, Ali I, Ahmad S, Khan SU, Hussain T, Ullah M, Lu K. Single-cell RNA Sequencing (scRNA-seq): Advances and Challenges for Cardiovascular Diseases (CVDs). Curr Probl Cardiol 2024; 49:102202. [PMID: 37967800 DOI: 10.1016/j.cpcardiol.2023.102202] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 11/11/2023] [Indexed: 11/17/2023]
Abstract
Implementing Single-cell RNA sequencing (scRNA-seq) has significantly enhanced our comprehension of cardiovascular diseases (CVDs), providing new opportunities to strengthen the prevention of CVDs progression. Cardiovascular diseases continue to be the primary cause of death worldwide. Improving treatment strategies and patient risk assessment requires a deeper understanding of the fundamental mechanisms underlying these disorders. The advanced and widespread use of Single-cell RNA sequencing enables a comprehensive investigation of the complex cellular makeup of the heart, surpassing essential descriptive aspects. This enhances our understanding of disease causes and directs functional research. The significant advancement in understanding cellular phenotypes has enhanced the study of fundamental cardiovascular science. scRNA-seq enables the identification of discrete cellular subgroups, unveiling previously unknown cell types in the heart and vascular systems that may have relevance to different disease pathologies. Moreover, scRNA-seq has revealed significant heterogeneity in phenotypes among distinct cell subtypes. Finally, we will examine current and upcoming scRNA-seq studies about various aspects of the cardiovascular system, assessing their potential impact on our understanding of the cardiovascular system and offering insight into how these technologies may revolutionise the diagnosis and treatment of cardiac conditions.
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Affiliation(s)
- Shahid Ullah Khan
- Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, College of Agronomy and Biotechnology, Southwest University, Chongqing, 400715, China; Engineering Research Center of South Upland Agriculture, Ministry of Education, Chongqing, 400715, China; Women Medical and Dental College, Khyber Medical University, Peshawar, KPK, 22020, Pakistan
| | - Yuqing Huang
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, China; Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hamid Ali
- Department of Biosciences, COMSATS University Islamabad, Park Road Tarlai Kalan, Islamabad-44000
| | - Ijaz Ali
- Centre for Applied Mathematics and Bioinformatics, Gulf University for Science and Technology, Hawally 32093, Kuwait
| | - Saleem Ahmad
- Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans 70112 LA, USA
| | - Safir Ullah Khan
- Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, People's Republic of China
| | - Talib Hussain
- Women Dental College Abbottabad, KPK, 22020, Pakistan
| | - Muneeb Ullah
- Department of Pharmacy, Kohat University of Science and Technology, Kohat, KPK, Pakistan
| | - Kun Lu
- Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, College of Agronomy and Biotechnology, Southwest University, Chongqing, 400715, China; Engineering Research Center of South Upland Agriculture, Ministry of Education, Chongqing, 400715, China.
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Silnitsky S, Rubin SJS, Zerihun M, Qvit N. An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases. Int J Mol Sci 2023; 24:17600. [PMID: 38139428 PMCID: PMC10743896 DOI: 10.3390/ijms242417600] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 12/10/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Protein kinases are one of the most significant drug targets in the human proteome, historically harnessed for the treatment of cancer, cardiovascular disease, and a growing number of other conditions, including autoimmune and inflammatory processes. Since the approval of the first kinase inhibitors in the late 1990s and early 2000s, the field has grown exponentially, comprising 98 approved therapeutics to date, 37 of which were approved between 2016 and 2021. While many of these small-molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP binding pocket have been massively successful for oncological indications, their poor selectively for protein kinase isozymes have limited them due to toxicities in their application to other disease spaces. Thus, recent attention has turned to the use of alternative allosteric binding mechanisms and improved drug platforms such as modified peptides to design protein kinase modulators with enhanced selectivity and other pharmacological properties. Herein we review the role of different protein kinase C (PKC) isoforms in cancer and cardiovascular disease, with particular attention to PKC-family inhibitors. We discuss translational examples and carefully consider the advantages and limitations of each compound (Part I). We also discuss the recent advances in the field of protein kinase modulators, leverage molecular docking to model inhibitor-kinase interactions, and propose mechanisms of action that will aid in the design of next-generation protein kinase modulators (Part II).
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Affiliation(s)
- Shmuel Silnitsky
- The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold St. 8, Safed 1311502, Israel; (S.S.); (M.Z.)
| | - Samuel J. S. Rubin
- Department of Medicine, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA;
| | - Mulate Zerihun
- The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold St. 8, Safed 1311502, Israel; (S.S.); (M.Z.)
| | - Nir Qvit
- The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold St. 8, Safed 1311502, Israel; (S.S.); (M.Z.)
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Kapıcı Y, Tanrıverdi Z, Tekin A, Güc B, Abuş S, Karamustafalıoğlu O. Comparison of frontal QRS-T angle and inflammatory parameters between the patients with drug-naive first episode psychosis and healthy controls. J Electrocardiol 2023; 81:106-110. [PMID: 37677849 DOI: 10.1016/j.jelectrocard.2023.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 08/08/2023] [Accepted: 08/23/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Frontal QRS-T (fQRS-T) angle is a novel marker to predict many cardiovascular diseases. The present study aims to compare the fQRS-T angle of first episode psychosis (FEP) patients and healthy controls (HC) and evaluate the relationship between fQRS-T angle and blood count-related inflammatory markers such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to high-density lipoprotein cholesterol ratio (MHR). METHODS Electrocardiogram (ECG) and complete blood count (CBC) of 63 patients who were diagnosed with drug-naive FEP in the psychiatry clinic of a training and research hospital and 78 healthy controls (HC) individuals who had applied to the health committee polyclinic for recruitment or pre-military examination between 2016 and 2021 were included. RESULTS fQRS-T angle was wider in FEP patients (55.5o) than in healthy controls (22o) (p < .001). NLR, PLR, and MHR were higher in FEP patients than in healthy controls (p = .001, p < .001, and p < .001, respectively). fQRS-T angle was positively correlated with NLR (r = 0.52 and p < .001) and MHR (r = 0.39 and p = .002) in FEP patients. NLR (t = 2.196 and p = .032) and MHR (t = 5.469 and p < .001) values were found to be the predictors of fQRS-T angle in FEP patients. CONCLUSION In summary, we can conclude that patients with FEP tend to exhibit a wider fQRS-T angle compared to their healthy controls. Additionally, the values of NLR and MHR could potentially serve as useful indicators for predicting the fQRS-T angle in FEP patients. Conducting subsequent long-term studies could provide deeper insights into the interpretation of the fQRS-T angle and its potential connection to cardiovascular diseases in schizophrenia patients.
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Affiliation(s)
- Yaşar Kapıcı
- Kahta State Hospital, Psychiatry Department, Adıyaman, Turkey.
| | - Zülkif Tanrıverdi
- Harran University, Faculty of Medicine, Cardiology Department, Şanlıurfa, Turkey
| | - Atilla Tekin
- Adıyaman University, Faculty of Medicine, Psychiatry Department, Adıyaman, Turkey
| | - Bulut Güc
- Şanlıurfa Balıklıgöl State Hospital, Psychiatry Department, Şanlıurfa, Turkey
| | - Sabri Abuş
- Adıyaman Education and Research Hospital, Cardiology Department, Adıyaman, Turkey
| | - Oğuz Karamustafalıoğlu
- Psychiatry, İstanbul University-Cerrahpaşa, Institue of Forensic Sciences, İstanbul, Turkey
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Kitazaki Y, Yamamura O, Usui K, Ueno A, Sanada S, Sasaki H, Endo Y, Enomoto S, Ikawa M, Nakamoto Y, Hamano T. Anti-Kv1.4 Antibody-positive Nivolumab-induced Myasthenia Gravis and Myositis Presenting with Bilateral Ptosis and Demonstrating Different Pathophysiologies. Intern Med 2023; 62:3013-3020. [PMID: 37839874 PMCID: PMC10641203 DOI: 10.2169/internalmedicine.0739-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/21/2022] [Indexed: 10/17/2023] Open
Abstract
Nivolumab blocks inhibitors of T-cell activation and restores antitumor immunity but promotes T-cell activity in host tissues by blocking inhibition of the T-cell function, resulting in immune-related adverse effects. We herein report an 80-year-old man presenting with nivolumab-related myasthenia gravis with anti-muscular voltage-gated potassium channel-complex (Kv1.4) antibodies. On day 29 after nivolumab administration, he simultaneously developed rapidly progressing right ptosis and left facial paralysis. Nivolumab administration was discontinued. He subsequently presented with bulbar paralysis, dyspnea, and muscle weakness and received intravenous immunoglobulin, methylprednisolone, and plasma exchange. The severity of nivolumab-related myasthenia gravis with anti-Kv1.4 antibodies presented with diverse clinical findings.
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Affiliation(s)
- Yuki Kitazaki
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Osamu Yamamura
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
- Department of Community Medicine, Faculty of Medical Science, University of Fukui, Japan
| | - Kojiro Usui
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Asako Ueno
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
- Department of Neurology, Fukui-ken Saiseikai Hospital, Japan
| | - Sayaka Sanada
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Hirohito Sasaki
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Yoshinori Endo
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Soichi Enomoto
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Masamichi Ikawa
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
- Department of Advanced Medicine for Community Healthcare, Faculty of Medical Sciences, University of Fukui, Japan
| | - Yasunari Nakamoto
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
| | - Tadanori Hamano
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Japan
- Department of Aging and Dementia, Faculty of Medical Sciences, University of Fukui, Japan
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Huynh K. Novel macrophage targets for the treatment of atrial fibrillation. Nat Rev Cardiol 2023; 20:648. [PMID: 37532948 DOI: 10.1038/s41569-023-00918-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/04/2023]
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Simon-Chica A, Wülfers EM, Kohl P. Nonmyocytes as electrophysiological contributors to cardiac excitation and conduction. Am J Physiol Heart Circ Physiol 2023; 325:H475-H491. [PMID: 37417876 PMCID: PMC10538996 DOI: 10.1152/ajpheart.00184.2023] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 06/22/2023] [Accepted: 06/29/2023] [Indexed: 07/08/2023]
Abstract
Although cardiac action potential (AP) generation and propagation have traditionally been attributed exclusively to cardiomyocytes (CM), other cell types in the heart are also capable of forming electrically conducting junctions. Interactions between CM and nonmyocytes (NM) enable and modulate each other's activity. This review provides an overview of the current understanding of heterocellular electrical communication in the heart. Although cardiac fibroblasts were initially thought to be electrical insulators, recent studies have demonstrated that they form functional electrical connections with CM in situ. Other NM, such as macrophages, have also been recognized as contributing to cardiac electrophysiology and arrhythmogenesis. Novel experimental tools have enabled the investigation of cell-specific activity patterns in native cardiac tissue, which is expected to yield exciting new insights into the development of novel or improved diagnostic and therapeutic strategies.
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Affiliation(s)
- Ana Simon-Chica
- Novel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
| | - Eike M Wülfers
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Department of Physics and Astronomy, Faculty of Sciences, Ghent University, Gent, Belgium
| | - Peter Kohl
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Jiahao L, Shuixian L, Keshun Y, Bohua Z. An end-end arrhythmia diagnosis model based on deep learning neural network with multi-scale feature extraction. Phys Eng Sci Med 2023; 46:1341-1352. [PMID: 37393423 DOI: 10.1007/s13246-023-01286-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 05/22/2023] [Indexed: 07/03/2023]
Abstract
This study presents an innovative end-to-end deep learning arrhythmia diagnosis model that aims to address the problems in arrhythmia diagnosis. The model performs pre-processing of the heartbeat signal by automatically and efficiently extracting time-domain, time-frequency-domain and multi-scale features at different scales. These features are imported into an adaptive online convolutional network-based classification inference module for arrhythmia diagnosis. Experimental results show that the AOCT-based deep learning neural network diagnostic module has excellent parallel computing and classification inference capabilities, and the overall performance of the model improves with increasing scales. In particular, when multi-scale features are used as inputs, the model is able to learn both time-frequency domain information and other rich information, thus significantly improving the performance of the end-to-end diagnostic model. The final results show that the AOCT-based deep learning neural network model has an average accuracy of 99.72%, a recall of 99.62%, and an F1 score of 99.3% in diagnosing four common heart diseases.
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Affiliation(s)
- Li Jiahao
- Ganzhou Polytechnic, Zhanggong District, Ganzhou City, 341099, Jiangxi Province, China
| | - Luo Shuixian
- The First Affiliated Hospital of Gannan Medical College, No. 23, Qingnian Road, Ganzhou City, 341001, Jiangxi Province, China
| | - You Keshun
- Jiangxi University of Science and Technology, 1958 Hakka Avenue, Ganzhou City, 341000, Jiangxi Province, China.
| | - Zen Bohua
- Ganzhou Polytechnic, Zhanggong District, Ganzhou City, 341099, Jiangxi Province, China
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Abstract
The cardiovascular system is hardwired to the brain via multilayered afferent and efferent polysynaptic axonal connections. Two major anatomically and functionally distinct though closely interacting subcircuits within the cardiovascular system have recently been defined: The artery-brain circuit and the heart-brain circuit. However, how the nervous system impacts cardiovascular disease progression remains poorly understood. Here, we review recent findings on the anatomy, structures, and inner workings of the lesser-known artery-brain circuit and the better-established heart-brain circuit. We explore the evidence that signals from arteries or the heart form a systemic and finely tuned cardiovascular brain circuit: afferent inputs originating in the arterial tree or the heart are conveyed to distinct sensory neurons in the brain. There, primary integration centers act as hubs that receive and integrate artery-brain circuit-derived and heart-brain circuit-derived signals and process them together with axonal connections and humoral cues from distant brain regions. To conclude the cardiovascular brain circuit, integration centers transmit the constantly modified signals to efferent neurons which transfer them back to the cardiovascular system. Importantly, primary integration centers are wired to and receive information from secondary brain centers that control a wide variety of brain traits encoded in engrams including immune memory, stress-regulating hormone release, pain, reward, emotions, and even motivated types of behavior. Finally, we explore the important possibility that brain effector neurons in the cardiovascular brain circuit network connect efferent signals to other peripheral organs including the immune system, the gut, the liver, and adipose tissue. The enormous recent progress vis-à-vis the cardiovascular brain circuit allows us to propose a novel neurobiology-centered cardiovascular disease hypothesis that we term the neuroimmune cardiovascular circuit hypothesis.
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Affiliation(s)
- Sarajo K Mohanta
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-University (LMU), Munich, Germany (S.K.M., C.Y., C.W., A.J.R.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance (S.K.M., C.W., A.J.R.H.)
| | - Changjun Yin
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-University (LMU), Munich, Germany (S.K.M., C.Y., C.W., A.J.R.H.)
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China (C.Y.)
| | - Christian Weber
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-University (LMU), Munich, Germany (S.K.M., C.Y., C.W., A.J.R.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance (S.K.M., C.W., A.J.R.H.)
| | - Cristina Godinho-Silva
- Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal (C.G.-S., H.V.-F.)
| | | | - Qian J Xu
- Department of Neuroscience, Department of Cellular and Molecular Physiology, Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT (Q.J.X., R.B.C.)
| | - Rui B Chang
- Department of Neuroscience, Department of Cellular and Molecular Physiology, Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT (Q.J.X., R.B.C.)
| | - Andreas J R Habenicht
- Institute for Cardiovascular Prevention, Ludwig-Maximilians-University (LMU), Munich, Germany (S.K.M., C.Y., C.W., A.J.R.H.)
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance (S.K.M., C.W., A.J.R.H.)
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Sheng Y, Carpenter JS, Paul SM, Conley YP, Levine JD, Miaskowski C. Patients with palpitations experience a higher symptom burden prior to breast cancer surgery. Eur J Oncol Nurs 2023; 65:102341. [PMID: 37327556 DOI: 10.1016/j.ejon.2023.102341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 04/11/2023] [Accepted: 04/29/2023] [Indexed: 06/18/2023]
Abstract
PURPOSE Anxiety, depression, sleep disturbance, fatigue, cognitive dysfunction, and pain are common symptoms reported by patients with breast cancer. Recent evidence suggests that palpitations, a feeling of the heart racing or pounding, may be equally common. Study purpose was to compare the severity and clinically meaningful occurrence rates of common symptoms and quality of life (QOL) outcomes between patients with breast cancer who did and did not report palpitations prior to surgery. METHODS Patients (n = 398) were classified as having or not having palpitations using a single item from the Menopausal Symptoms Scale. Valid and reliable measures were used to assess state and trait anxiety, depression, sleep disturbance, fatigue, energy, cognitive function, breast symptoms, and QOL. Between group differences were evaluated using parametric and non-parametric tests. RESULTS Patients with palpitations (15.1%) reported significantly higher severity scores for state and trait anxiety, depression, sleep disturbance, and fatigue as well as significant decrements in energy and cognitive function (all p < .05). A higher percentage of these patients had clinically meaningful levels of state anxiety, depression, sleep disturbance and decrements in cognitive function (all p < .05). Except for spiritual well-being, QOL scores were lower in the palpitations group (all p < .001). CONCLUSION Findings support the need for routine assessment of palpitations and management of multiple symptoms in women prior to breast cancer surgery.
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Affiliation(s)
- Ying Sheng
- School of Nursing, Indiana University, Indianapolis, IN, USA
| | | | - Steven M Paul
- School of Nursing, University of California at San Francisco, San Francisco, CA, USA
| | - Yvette P Conley
- School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jon D Levine
- School of Medicine, University of California at San Francisco, San Francisco, CA, USA
| | - Christine Miaskowski
- School of Nursing, University of California at San Francisco, San Francisco, CA, USA; School of Medicine, University of California at San Francisco, San Francisco, CA, USA.
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Chen Y, Lou L, Zhang X, Jin L, Chen Y, Chen L, Li Z, Zhang F, Fu T, Hu S, Yang J. Association between circulating leukocytes and arrhythmias: Mendelian randomization analysis in immuno-cardiac electrophysiology. Front Immunol 2023; 14:1041591. [PMID: 37090734 PMCID: PMC10113438 DOI: 10.3389/fimmu.2023.1041591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 03/24/2023] [Indexed: 04/07/2023] Open
Abstract
BackgroundCardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence.Methods and findingsWe performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11–1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation.ConclusionOur data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.
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Affiliation(s)
- Yuxiao Chen
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lian Lou
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Zhang
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Luyang Jin
- Department of Gynecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yao Chen
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lele Chen
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhihang Li
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Fen Zhang
- Department of Cardiology, Jinhua People's Hospital, Jinhua, China
| | - Ting Fu
- Department of Cardiology, Yiwu Central Hospital, Jinhua, China
| | - Shenjiang Hu
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Yang
- Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Wang MF, Xue C, Shi SY, Yang L, Zhu ZY, Li JJ. Gene Polymorphism and Recurrent Atrial Fibrillation after Catheter Ablation: A Comprehensive Review. Rev Cardiovasc Med 2023; 24:119. [PMID: 39076272 PMCID: PMC11273024 DOI: 10.31083/j.rcm2404119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/11/2022] [Accepted: 12/19/2022] [Indexed: 08/15/2023] Open
Abstract
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, but its pathogenesis is still poorly understood. Catheter ablation is one of the most effective treatments for AF, but recurrence after ablation remains a challenge. There has been much research into the association of AF recurrence with several factors, including genetics. Over the past decade or so, significant advances have been made in the genetic architecture of atrial fibrillation. Genome-wide association studies (GWAS) have identified over 100 loci for genetic variants associated with atrial fibrillation. However, there is relatively little information on the systematic assessment of the genes related to AF recurrence after ablation. In this review article, we highlight the value of genetic polymorphisms in atrial fibrillation recurrence after catheter ablation and their potential mechanisms in the recurrence process to enhance our understanding of atrial fibrillation recurrence and contribute to individualized treatment strategies for patients with AF.
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Affiliation(s)
- Meng-Fei Wang
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, 213000 Changzhou, Jiangsu, China
| | - Cong Xue
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, 213000 Changzhou, Jiangsu, China
| | - Shun-Yi Shi
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, 213000 Changzhou, Jiangsu, China
| | - Ling Yang
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, 213000 Changzhou, Jiangsu, China
| | - Zhen-Yan Zhu
- Department of Cardiology, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, 213000 Changzhou, Jiangsu, China
| | - Jian-Jun Li
- State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 100037 Beijing, China
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Anti-Kv1.4 Antibody Without Myasthenia Gravis: A Rare Cause of Autoimmune Myocarditis and Myositis. JACC Case Rep 2023; 9:101734. [PMID: 36909266 PMCID: PMC9998724 DOI: 10.1016/j.jaccas.2023.101734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 01/28/2023]
Abstract
Anti-Kv1.4 antibody is often detected in thymoma-associated myasthenia gravis patients with anti-acetylcholine receptor antibody. Herein, we describe 2 patients with concurrent myocarditis and myositis. In both cases, anti-Kv1.4 antibody was positive despite the absence of thymoma and anti-acetylcholine receptor antibody, and immunosuppressants eventually resolved their symptoms and cardiac function. (Level of Difficulty: Advanced.).
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La Cognata O, Trimarchi G, Lo Savio A, Virga V, Andò G, de Gregorio C. Kounis syndrome in a patient with multivessel coronary artery disease and DRESS. Clin Case Rep 2023; 11:e7121. [PMID: 36950673 PMCID: PMC10025948 DOI: 10.1002/ccr3.7121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/20/2023] [Accepted: 03/08/2023] [Indexed: 03/24/2023] Open
Abstract
A 68-year-old man was admitted with ST-elevation myocardial infarction and intense rash. He was diagnosed with type 2 Kounis syndrome elicited by drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and received complete revascularization with percutaneous coronary intervention. This case highlights the complex pathophysiology of acute coronary syndrome, and the elusive link between coronary occlusion and ST-segment deviations at ECG.
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Affiliation(s)
- Olga La Cognata
- Department of Clinical and Experimental Medicine, Postgraduate School of CardiologyAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of MessinaMessinaItaly
| | - Giancarlo Trimarchi
- Department of Clinical and Experimental Medicine, Postgraduate School of CardiologyAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of MessinaMessinaItaly
| | - Armando Lo Savio
- Department of Clinical and Experimental Medicine, Postgraduate School of CardiologyAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of MessinaMessinaItaly
| | - Vittorio Virga
- Department of Clinical and Experimental Medicine, Postgraduate School of CardiologyAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of MessinaMessinaItaly
| | - Giuseppe Andò
- Department of Clinical and Experimental Medicine, Postgraduate School of CardiologyAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of MessinaMessinaItaly
| | - Cesare de Gregorio
- Department of Clinical and Experimental Medicine, Postgraduate School of CardiologyAzienda Ospedaliera Universitaria Policlinico “Gaetano Martino”, University of MessinaMessinaItaly
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Shogase T, Ohtsuru S, Morita Y, Osaki Y, Furuya H, Anayama T. [A case of non-thymomatous refractory anti-AChR, Kv1.4 and titin antibodies positive generalized myasthenia gravis successfully treated by extended thymectomy]. Rinsho Shinkeigaku 2023; 63:92-96. [PMID: 36725010 DOI: 10.5692/clinicalneurol.cn-001813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
A 74-year-old Japanese woman, who had been previously diagnosed as ocular myasthenia gravis (MG), presented to our hospital complaining of dropped head and increased fatiguability while eating. The edrophonium test was positive and decremental response was recorded on repetitive nerve stimulation. Her clinical presentation was compatible with generalized MG, and anti-AChR, Kv1.4 and titin antibodies turned out positive. Contrast enhanced CT scan showed no tumorous lesion such as thymoma. We initiated her treatment with a minimum dose of oral prednisolone. However, her condition got worse even after intravenous immune globulin and experienced myasthenic crisis twice, the former of which led to cardiopulmonary arrest. As she did not respond to traditional treatments, we determined to perform extended thymectomy. The histopathology showed atrophic change but her condition rapidly improved in several days after the operation, and soon she was weaned off the ventilator. Shortly thereafter her symptoms disappeared, followed by the titers of the antibodies above found all markedly decreased. It remains unclear how the atrophic thymus acted on the pathogenesis of refractory generalized MG.
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Affiliation(s)
| | - Sho Ohtsuru
- Department of Neurology, Kochi Medical School Hospital
| | - Yukari Morita
- Department of Neurology, Kochi Medical School Hospital
| | - Yasushi Osaki
- Department of Neurology, Kochi Medical School Hospital
| | | | - Takashi Anayama
- Department of Respiratory surgery, Kochi Medical School Hospital
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Zhang J, Li H, Wang D, Gu J, Hou Y, Wu Y. Shensong Yangxin Capsule Reduces the Susceptibility of Arrhythmia in db/db Mice via Inhibiting the Inflammatory Response Induced by Endothelium Dysfunction. Drug Des Devel Ther 2023; 17:313-330. [PMID: 36776448 PMCID: PMC9912345 DOI: 10.2147/dddt.s392328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 01/14/2023] [Indexed: 02/05/2023] Open
Abstract
Purpose The aim of our study was to investigate the mechanism by which the Chinese compound Shensong Yangxin Capsule (SSYX) reduces susceptibility to arrhythmia in db/db mice. Methods The db/db mice without drug treatment served as the model group. Other-treated db/db mice were administered SSYX for 8 weeks. Electrocardiogram (ECG), electrical mapping, pathological changes, immunofluorescence staining, real-time quantitative PCR, and Western blot analyses were then conducted. Results SSYX decreased arrhythmia susceptibility and shortened the abnormal ECG parameters of db/db mice. Meanwhile, SSYX restored irregular conduction direction and shortened the conduction time of the isolated heart. HE and Masson staining showed that SSYX alleviated inflammatory infiltration and collagen fiber deposition. Western blot showed that SSYX decreased the protein expression of ICAM-1, VCAM-1, and MCP-1 and increased the protein expression of occludin, ZO-1, eNOS, and Cx43. SSYX also increased the content of NO, decreased ET-1, TNF-α, IL-1β, IL-6, MCP-1, and CCR-2 mRNA expression, and increased Kv 4.2, Kv 4.3, Cav 1.2, and Nav 1.5 mRNA expression. Furthermore, SSYX decreased the fluorescence intensity of F4/80 and iNOS, increased the fluorescence intensity of CD31 and eNOS, and improved the Cx43 and α-actinin connection structure in cardiac tissues. The above therapeutic effects of SSYX were inhibited by L-NAME. Conclusion SSYX reduced the susceptibility of db/db mice to arrhythmia by inhibiting the inflammatory response and macrophage polarization, and this effect of SSYX occurred through protection of endothelial cell function.
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Affiliation(s)
- Jiehan Zhang
- Hebei Medical University, Shijiazhuang, People’s Republic of China,National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Hongrong Li
- Key Laboratory of State Administration of TCM (Cardio-Cerebral Vessel Collateral Disease), Shijiazhuang, People’s Republic of China,Hebei Yiling Hospital, Shijiazhuang, People’s Republic of China
| | - Dandong Wang
- Hebei Medical University, Shijiazhuang, People’s Republic of China,National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Jiaojiao Gu
- National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Shijiazhuang, People’s Republic of China,Hebei University of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Yunlong Hou
- Hebei Medical University, Shijiazhuang, People’s Republic of China,National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Shijiazhuang, People’s Republic of China
| | - Yiling Wu
- Hebei Medical University, Shijiazhuang, People’s Republic of China,National Key Laboratory of Collateral Disease Research and Innovative Chinese Medicine, Shijiazhuang, People’s Republic of China,Correspondence: Yiling Wu; Yunlong Hou, Hebei Medical University, Shijiazhuang, People’s Republic of China, Email ;
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Goette A, Lip GYH, Gorenek B. What acute cardiac care physicians need to know from the latest 2022 ESC Guidelines for ventricular tachycardia and sudden cardiac death. EUROPEAN HEART JOURNAL. ACUTE CARDIOVASCULAR CARE 2023; 12:62-68. [PMID: 36449983 DOI: 10.1093/ehjacc/zuac149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 11/23/2022] [Indexed: 12/03/2022]
Abstract
The present paper summarizes and comments on the latest 2022 ESC guidelines on ventricular tachycardia and sudden cardiac death. Most relevant recommendations for acute cardiovascular care physicians are addressed, particularly, in the fields of coronary artery disease, dilated cardiomyopathy, and inflammatory diseases. New recommendations encompass the implantation of a defibrillator (ICD) in the setting of acute myocarditis. Furthermore, the pathophysiology of the electrical storm including involved molecular pathways as well as the angry Purkinje fibre syndrome is presented and discussed.
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Affiliation(s)
- Andreas Goette
- Department of Cardiology and Intensive Care Medicine, St. Vincenz Hospital, 33098 Paderborn, Germany.,Association for Acute CardioVascular Care: Task Force Acute Rhythm Disturbances, European Society of Cardiology, 2035 Rte des Colles, 06410 Biot, France
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Thomas Drive, Liverpool L14 3PE, UK.,Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Sondra Skovvej, 15, Aalborg 9000, Denmark
| | - Bulent Gorenek
- Association for Acute CardioVascular Care: Task Force Acute Rhythm Disturbances, European Society of Cardiology, 2035 Rte des Colles, 06410 Biot, France.,School of Medicine, Cardiology Department, Eskisehir Osmangazi University, Meselik, 26480 Eskişehir, Turkey
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Jiang X, Ning P, Yan F, Wang J, Cai W, Yang F. Impact of myeloid differentiation protein 1 on cardiovascular disease. Biomed Pharmacother 2023; 157:114000. [PMID: 36379121 DOI: 10.1016/j.biopha.2022.114000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/13/2022] Open
Abstract
Cardiovascular disease remains the leading cause of disability and mortality worldwide and a significant global burden. Many lines of evidence suggest complex remodeling responses to cardiovascular disease, such as myocardial ischemia, hypertension and valve disease, which lead to poor clinical outcomes, including heart failure, arrhythmia and sudden cardiac death (SCD). The mechanisms underlying cardiac remodeling are closely related to reactive oxygen species (ROS) and inflammation. Myeloid differentiation protein 1 (MD1) is a secreted glycoprotein known as lymphocyte antigen 86. The complex of MD1 and radioprotective 105 (RP105) is an important regulator of inflammation and is involved in the modulation of vascular remodeling and atherosclerotic plaque development. A recent study suggested that the expression of MD1 in hypertrophic cardiomyopathy (HCM) patients is decreased compared with that in donor hearts. Therefore, MD1 may play an important role in the pathological processes of cardiovascular disease and have potential clinical value. Here, this review aims to discuss the current knowledge regarding the role of MD1 in the regulation of cardiac pathophysiology.
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Affiliation(s)
- Xiaobo Jiang
- Geriatric Diseases Institute of Chengdu, Department of Cardiology, Chengdu Fifth People's Hospital, Chengdu 611137, China; The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Peng Ning
- The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Geriatric Diseases Institute of Chengdu, Department of Endocrinology, Chengdu Fifth People's Hospital, Chengdu 611137, China.
| | - Fang Yan
- Geriatric Department, Chengdu Fifth People's Hospital, Chengdu 611137, China; Center for Medicine Research and Translation, Chengdu Fifth People's Hospital, Chengdu 611137, China.
| | - Jianfeng Wang
- Geriatric Diseases Institute of Chengdu, Department of Cardiology, Chengdu Fifth People's Hospital, Chengdu 611137, China; The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Wei Cai
- Geriatric Diseases Institute of Chengdu, Department of Cardiology, Chengdu Fifth People's Hospital, Chengdu 611137, China; The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Fan Yang
- The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Geriatric Diseases Institute of Chengdu, Department of Endocrinology, Chengdu Fifth People's Hospital, Chengdu 611137, China.
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Xing C, Bao L, Li W, Fan H. Progress on role of ion channels of cardiac fibroblasts in fibrosis. Front Physiol 2023; 14:1138306. [PMID: 36969589 PMCID: PMC10033868 DOI: 10.3389/fphys.2023.1138306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 02/27/2023] [Indexed: 03/29/2023] Open
Abstract
Cardiac fibrosis is defined as excessive deposition of extracellular matrix (ECM) in pathological conditions. Cardiac fibroblasts (CFs) activated by injury or inflammation differentiate into myofibroblasts (MFs) with secretory and contractile functions. In the fibrotic heart, MFs produce ECM which is composed mainly of collagen and is initially involved in maintaining tissue integrity. However, persistent fibrosis disrupts the coordination of excitatory contractile coupling, leading to systolic and diastolic dysfunction, and ultimately heart failure. Numerous studies have demonstrated that both voltage- and non-voltage-gated ion channels alter intracellular ion levels and cellular activity, contributing to myofibroblast proliferation, contraction, and secretory function. However, an effective treatment strategy for myocardial fibrosis has not been established. Therefore, this review describes the progress made in research related to transient receptor potential (TRP) channels, Piezo1, Ca2+ release-activated Ca2+ (CRAC) channels, voltage-gated Ca2+ channels (VGCCs), sodium channels, and potassium channels in myocardial fibroblasts with the aim of providing new ideas for treating myocardial fibrosis.
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50
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Zhang L, Liu HH, Li F, Yang F, Qian LL, Wang RX. The Role of NLRP3 Inflammasome Signaling on Arrhythmias in Diabetes. J Inflamm Res 2022; 15:6883-6889. [PMID: 36600995 PMCID: PMC9807127 DOI: 10.2147/jir.s390310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/16/2022] [Indexed: 12/29/2022] Open
Abstract
Diabetes is a significant risk factor for arrhythmias. However, the pathophysiology of diabetes-related arrhythmias still needs to be elucidated, presumably associated with structural and electrical remodeling. There is growing evidence that inflammation and arrhythmias are intimately associated, which has spurred significant interest in exploring the regulatory links in diabetes. Recent research findings have revealed a vital role for the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling, and facilitated the occurrence of arrhythmias in diabetes, including NLRP3 inflammasome activation by multiple stressors and its downstream cytokines, interleukin-1β (IL-1β) and interleukin-18 (IL-18). This narrative review aims to summarize the complex interaction between NLRP3 inflammasomes signaling and diabetes-related arrhythmias. Articles regarding the role of NLRP3 inflammasome in diabetes-related arrhythmias and relevant mechanisms were selected. Relevant articles were selected from PubMed. The search terms were "NLRP3 inflammasome" and "diabetes" and "arrhythmia". Important references from selected articles were also retrieved. The role of NLRP3 inflammasome signaling in diabetes-induced arrhythmias may provide a new option for the prevention and treatment diabetes-related arrhythmias.
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Affiliation(s)
- Lei Zhang
- Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China
| | - Huan-Huan Liu
- Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China
| | - Feng Li
- Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China
| | - Fan Yang
- Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China
| | - Ling-Ling Qian
- Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China
| | - Ru-Xing Wang
- Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, People’s Republic of China,Correspondence: Ru-Xing Wang, Tel +86-510-85351593, Fax +86-510-85350555, Email
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