|
1
|
Panwar A, Malik SO, Adib M, Lopaschuk GD. Cardiac energy metabolism in diabetes: emerging therapeutic targets and clinical implications. Am J Physiol Heart Circ Physiol 2025; 328:H1089-H1112. [PMID: 40192025 DOI: 10.1152/ajpheart.00615.2024] [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: 09/06/2024] [Revised: 10/15/2024] [Accepted: 04/01/2025] [Indexed: 04/25/2025]
Abstract
Patients with diabetes are at an increased risk for developing diabetic cardiomyopathy and other cardiovascular complications. Alterations in cardiac energy metabolism in patients with diabetes, including an increase in mitochondrial fatty acid oxidation and a decrease in glucose oxidation, are important contributing factors to this increase in cardiovascular disease. A switch from glucose oxidation to fatty acid oxidation not only decreases cardiac efficiency due to increased oxygen consumption but it can also increase reactive oxygen species production, increase lipotoxicity, and redirect glucose into other metabolic pathways that, combined, can lead to heart dysfunction. Currently, there is a lack of therapeutics available to treat diabetes-induced heart failure that specifically target cardiac energy metabolism. However, it is becoming apparent that part of the benefit of existing agents such as GLP-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors may be related to their effects on cardiac energy metabolism. In addition, direct approaches aimed at inhibiting cardiac fatty acid oxidation or increasing glucose oxidation hold future promise as potential therapeutic approaches to treat diabetes-induced cardiovascular disease.
Collapse
Affiliation(s)
- Archee Panwar
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Sufyan O Malik
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Muhtasim Adib
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Gary D Lopaschuk
- Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
2
|
Hosseini Y, Niknejad A, Sabbagh Kashani A, Gholami M, Roustaie M, Mohammadi M, Momtaz S, Atkin SL, Jamialahmadi T, Abdolghaffari AH, Sahebkar A. NLRP3 inflammasomes pathway: a key target for Metformin. Inflammopharmacology 2025; 33:1729-1760. [PMID: 40042723 DOI: 10.1007/s10787-025-01702-4] [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: 01/04/2025] [Accepted: 01/31/2025] [Indexed: 04/13/2025]
Abstract
Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing 3 (NLRP3) is a signaling pathway that is involved in inflammatory cascades, cell survival and the immune response. NLRP3 is activated by cellular damage, oxidative stress, and other factors that stimulate the immune system. Stimulation of NLRP3 induces inflammatory reactions and the production of inflammatory cytokines. These inflammatory mediators are implicated in several diseases. Metformin (MET) is an anti-hyperglycemia agent that is extensively used in clinical practice worldwide due to its high efficiency, safety profile, and affordable price. MET is the only member of biguanide class that is used in clinical practice and a potent AMP-activated protein kinase (AMPK) agonist with proven anti-inflammatory characteristics. Due to its anti-inflammatory properties, MET is considered to be effective against diseases that have an inflammatory background, and the NLRP3 pathway is involved in the pathophysiology of these disorders. In this review, we have evaluated the evidence if MET can affect this pathway and its utility for future therapeutic approaches.
Collapse
Affiliation(s)
- Yasamin Hosseini
- Faculty of Pharmacy, Department of Toxicology and Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Amirhossein Niknejad
- Faculty of Pharmacy, Department of Toxicology and Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Ayeh Sabbagh Kashani
- Faculty of Pharmacy, Department of Toxicology and Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mahsa Gholami
- Faculty of Pharmacy, Department of Toxicology and Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mahtab Roustaie
- Faculty of Pharmacy, Department of Toxicology and Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | | | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
- Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
| | - Stephen L Atkin
- Royal College of Surgeons in Ireland, PO Box 15503, Adliya, Bahrain
| | - Tannaz Jamialahmadi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Hossein Abdolghaffari
- Faculty of Pharmacy, Department of Toxicology and Pharmacology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
- GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
3
|
Sgarra L, Desantis V, Matteucci A, Caccavo VP, Troisi F, Di Monaco A, Mangini F, Katsouras G, Guaricci AI, Dadamo ML, Fortunato F, Nacci C, Potenza MA, Montagnani M, Grimaldi M. Non-Anticoagulation Strategies Aimed at Primary Stroke Prevention in Nascent Atrial Fibrillation. Biomedicines 2025; 13:660. [PMID: 40149635 PMCID: PMC11939867 DOI: 10.3390/biomedicines13030660] [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: 01/16/2025] [Revised: 02/23/2025] [Accepted: 02/28/2025] [Indexed: 03/29/2025] Open
Abstract
At its earliest appearance, atrial fibrillation (AF) is often unnoticed, asymptomatic, and/or merely device-detected. Widespread use of heart-rate monitoring technologies has facilitated such "nascent atrial fibrillation (nAF)" recognition. Consequently, clinicians face a growing number of patients affected by new-onset AF in the absence of a definite indication for anticoagulation due to several counterarguments: (1) a CHA2DS2-VA score ≤ 1 in otherwise apparently healthy subjects; (2) an uncertain embolic/hemorrhagic benefit/risk ratio with anticoagulation; (3) EKG demonstration and confirmation of AF; and (4) existence of a pathogenic mechanism other than atrial hypercoagulability. In this frustrating limitation of pharmacological options, cardiologists may miss a complete comprehension of drugs with proven anti-ictal potential, whose administration may serve both as a bridge strategy toward future anticoagulation and as a consolidative strategy paralleling anticoagulation. This review aims to summarize and elucidate such therapeutic strategies and their preventative mechanisms.
Collapse
Affiliation(s)
- Luca Sgarra
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| | - Vanessa Desantis
- Pharmacology Section, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, 70124 Bari, Italy (M.M.)
| | - Andrea Matteucci
- Clinical and Rehabilitation Cardiology Unit, Emergency Department, San Filippo Neri Hospital, ASL Rome 1, 00135 Rome, Italy
- Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Vincenzo Paolo Caccavo
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| | - Federica Troisi
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| | - Antonio Di Monaco
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| | - Francesco Mangini
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| | - Grigorios Katsouras
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| | - Andrea Igoren Guaricci
- Cardiology Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, 70124 Bari, Italy
| | - Michele Luca Dadamo
- Cardiology Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, 70124 Bari, Italy
| | - Fabrizio Fortunato
- Department of Cardiology, Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone, 90127 Palermo, Italy
| | - Carmela Nacci
- Pharmacology Section, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, 70124 Bari, Italy (M.M.)
| | - Maria Assunta Potenza
- Pharmacology Section, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, 70124 Bari, Italy (M.M.)
| | - Monica Montagnani
- Pharmacology Section, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro Medical School, 70124 Bari, Italy (M.M.)
| | - Massimo Grimaldi
- Cardiology Unit, Medicine Department, General Hospital “F. Miulli” Acquaviva delle Fonti, 70021 Bari, Italy
| |
Collapse
|
|
4
|
Marunouchi T, Matsumura K, Sato K, Takeuchi S, Murakami T, Tanonaka K. Simvastatin and rosuvastatin attenuate necroptosis in rat failing hearts following myocardial infarction; the contribution of Hsp90 inhibition in cardiomyocytes to prevent necroptosis. Biochem Pharmacol 2025; 233:116792. [PMID: 39894308 DOI: 10.1016/j.bcp.2025.116792] [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: 07/23/2024] [Revised: 12/23/2024] [Accepted: 01/30/2025] [Indexed: 02/04/2025]
Abstract
Statins, a class of dyslipidemic drugs known as HMG-CoA reductase inhibitors, have emerged as promising compounds for the treatment of chronic heart failure. Nevertheless, the precise mechanism remains to be fully elucidated. Necroptosis is a programmed necrosis-like cell death and has been involved in the development of chronic heart failure. However, it is unclear whether statins exert beneficial effects on therapy for heart failure by inhibiting cardiomyocyte necroptosis. In this study, we administered statins to rats after myocardial infarction and evaluated their effects on the necroptosis pathway in the failing heart following myocardial infarction. Administration of simvastatin or rosuvastatin reduced cardiac dysfunction after myocardial infarction. Concomitantly, the statins prevented the activation of the necroptotic intracellular signaling pathway in myocardial tissue. Simvastatin, but not rosuvastatin treatment attenuated the interaction between Hsp90 and necroptosis-related proteins in myocardial tissue, suggesting that simvastatin prevents necroptosis via Hsp90 inhibition. Necroptosis induced in primary cultured cardiomyocytes isolated from neonatal rats was inhibited by pretreatment with simvastatin. Administration of simvastatin and rosuvastatin inhibited the infiltration of M1 macrophages into myocardial tissue and reduced the myocardial tissue content of tumor necrosis factor-α, an inflammatory cytokine that induces necroptosis, respectively. The findings in the study indicate that statins may prevent necroptosis of cardiomyocytes, attenuating the development of heart failure. However, the present study suggests that the cardioprotective mechanism of simvastatin is not same as that of rosuvastatin.
Collapse
Affiliation(s)
- Tetsuro Marunouchi
- Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan
| | - Kasumi Matsumura
- Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan
| | - Kaho Sato
- Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan
| | - Shiori Takeuchi
- Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan
| | - Takuma Murakami
- Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan
| | - Kouichi Tanonaka
- Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Japan.
| |
Collapse
|
|
5
|
Wu Q, Zeng Y, Geng K, Guo M, Teng FY, Yan PJ, Lei Y, Long Y, Jiang ZZ, Law BYK, Xu Y. The role of IL-1 family cytokines in diabetic cardiomyopathy. Metabolism 2025; 163:156083. [PMID: 39603339 DOI: 10.1016/j.metabol.2024.156083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 11/18/2024] [Accepted: 11/21/2024] [Indexed: 11/29/2024]
Abstract
Diabetic cardiomyopathy (DCM) is the primary cause of heart failure in patients with diabetes and is characterised by contractile dysfunction and left ventricular hypertrophy. The complex pathological and physiological mechanisms underlying DCM have contributed to a limited number of available treatment options. A substantial body of evidence has established that DCM is a low-grade inflammatory cardiovascular disorder, with the interleukin-1 (IL-1) family of cytokines playing crucial roles in initiating inflammatory responses and shaping innate and adaptive immunity. In this review, we aim to provide an overview of the underlying mechanisms of the IL-1 family and their relevance in DCM of various aetiologies. Furthermore, we highlighted potential therapeutic targets within the IL-1 family for the management of DCM.
Collapse
Affiliation(s)
- Qi Wu
- State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Department of Pathology, and Luzhou Key Laboratory of Precision Pathology Diagnosis for Serious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yan Zeng
- State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Kang Geng
- Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Department of Plastic and burns surgery, National Key Clinical Construction Specialty, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Man Guo
- Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Fang-Yuan Teng
- Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Pi-Jun Yan
- Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yi Lei
- State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yang Long
- Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Zong-Zhe Jiang
- Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Betty Yuen-Kwan Law
- State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China.
| | - Yong Xu
- State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Department of Endocrinology and Metabolism, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
| |
Collapse
|
|
6
|
Kakkar C, Sharma V, Mannan A, Gupta G, Singh S, Kumar P, Dua K, Kaur A, Singh S, Dhiman S, Singh TG. Diabetic Cardiomyopathy: An Update on Emerging Pathological Mechanisms. Curr Cardiol Rev 2025; 21:88-107. [PMID: 39501954 PMCID: PMC12060924 DOI: 10.2174/011573403x331870241025094307] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 09/03/2024] [Accepted: 10/09/2024] [Indexed: 04/25/2025] Open
Abstract
Diabetic Cardiomyopathy (DCM) is a notable consequence of diabetes mellitus, distinguished by cardiac dysfunction that occurs separately from coronary artery disease or hypertension. A recent study has revealed an intricate interaction of pathogenic processes that contribute to DCM. Important aspects involve the dysregulation of glucose metabolism, resulting in heightened oxidative stress and impaired mitochondrial function. In addition, persistent high blood sugar levels stimulate inflammatory pathways, which contribute to the development of heart fibrosis and remodelling. Additionally, changes in the way calcium is managed and the presence of insulin resistance are crucial factors in the formation and advancement of DCM. This may be due to the involvement of many molecular mechanistic pathways such as NLRP3, NF-κB, PKC, and MAPK with their downstream associated signaling pathways. Gaining a comprehensive understanding of these newly identified pathogenic pathways is crucial in order to design precise therapy approaches that can enhance the results for individuals suffering from diabetes. In addition, this review offers an in-depth review of not just pathogenic pathways and molecular mechanistic pathways but also diagnostic methods, treatment options, and clinical trials.
Collapse
Affiliation(s)
- Chirag Kakkar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Veerta Sharma
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Ashi Mannan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Gaurav Gupta
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, 346, United Arab Emirates
| | - Sachin Singh
- Lovely Institute of Technology (Pharmacy), Lovely Professional University, Phagwara, Punjab, India
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Broadway, P.O. Box 123, Ultimo, NSW, 2007, Australia
| | - Puneet Kumar
- Department of Pharmacology, School of Pharmaceutical Sciences, Central University of Punjab, Ghudda, Bathinda, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Broadway, P.O. Box 123, Ultimo, NSW, 2007, Australia
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Shareen Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Sonia Dhiman
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | | |
Collapse
|
|
7
|
Liu HJ, Gui LK, Wei H, Zhou XY, Liu ZL, Jin LJ. The role of NF-κB in diabetic cardiomyopathy. ALL LIFE 2024; 17. [DOI: 10.1080/26895293.2024.2397402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 08/20/2024] [Indexed: 01/03/2025] Open
Affiliation(s)
- Huang-Jun Liu
- Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China
| | - Le-Kun Gui
- Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China
- School of Medicine, Yangtze University, Jingzhou, People’s Republic of China
| | - Han Wei
- Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China
| | - Xing-Yu Zhou
- Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China
- School of Medicine, Yangtze University, Jingzhou, People’s Republic of China
| | - Zhen-Lan Liu
- Department of Anesthesiology, The First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China
| | - Li-Jun Jin
- Department of Cardiology, The First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China
| |
Collapse
|
|
8
|
Chen X, Yang Y, Zhou Z, Yu H, Zhang S, Huang S, Wei Z, Ren K, Jin Y. Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications. Int Immunopharmacol 2024; 141:112930. [PMID: 39146786 DOI: 10.1016/j.intimp.2024.112930] [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: 07/04/2024] [Revised: 07/26/2024] [Accepted: 08/10/2024] [Indexed: 08/17/2024]
Abstract
Cardiovascular diseases (CVDs) represent a significant public health concern because of their associations with inflammation, oxidative stress, and abnormal remodeling of the heart and blood vessels. In this review, we discuss the intricate interplay between mitochondria-associated membranes (MAMs) and cardiovascular inflammation, highlighting their role in key cellular processes such as calcium homeostasis, lipid metabolism, oxidative stress management, and ERS. We explored how these functions impact the pathogenesis and progression of various CVDs, including myocardial ischemia-reperfusion injury, atherosclerosis, diabetic cardiomyopathy, cardiovascular aging, heart failure, and pulmonary hypertension. Additionally, we examined current therapeutic strategies targeting MAM-related pathways and proteins, emphasizing the potential of MAMs as therapeutic targets. Our review aims to provide new insights into the mechanisms of cardiovascular inflammation and propose novel therapeutic approaches to improve cardiovascular health outcomes.
Collapse
Affiliation(s)
- Xing Chen
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Yang Yang
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Zheng Zhou
- Department of Geriatric Endocrinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Haihan Yu
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Shuwei Zhang
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Siyuan Huang
- Department of Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China
| | - Ziqing Wei
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
| | - Kaidi Ren
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
| | - Yage Jin
- Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.
| |
Collapse
|
|
9
|
Datta S, Pasham S, Inavolu S, Boini KM, Koka S. Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead. Int J Mol Sci 2024; 25:10208. [PMID: 39337693 PMCID: PMC11432476 DOI: 10.3390/ijms251810208] [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: 08/19/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of premature morbidity and mortality globally. The identification of novel risk factors contributing to CVD onset and progression has enabled an improved understanding of CVD pathophysiology. In addition to the conventional risk factors like high blood pressure, diabetes, obesity and smoking, the role of gut microbiome and intestinal microbe-derived metabolites in maintaining cardiovascular health has gained recent attention in the field of CVD pathophysiology. The human gastrointestinal tract caters to a highly diverse spectrum of microbes recognized as the gut microbiota, which are central to several physiologically significant cascades such as metabolism, nutrient absorption, and energy balance. The manipulation of the gut microbial subtleties potentially contributes to CVD, inflammation, neurodegeneration, obesity, and diabetic onset. The existing paradigm of studies suggests that the disruption of the gut microbial dynamics contributes towards CVD incidence. However, the exact mechanistic understanding of such a correlation from a signaling perspective remains elusive. This review has focused upon an in-depth characterization of gut microbial metabolites and their role in varied pathophysiological conditions, and highlights the potential molecular and signaling mechanisms governing the gut microbial metabolites in CVDs. In addition, it summarizes the existing courses of therapy in modulating the gut microbiome and its metabolites, limitations and scientific gaps in our current understanding, as well as future directions of studies involving the modulation of the gut microbiome and its metabolites, which can be undertaken to develop CVD-associated treatment options. Clarity in the understanding of the molecular interaction(s) and associations governing the gut microbiome and CVD shall potentially enable the development of novel druggable targets to ameliorate CVD in the years to come.
Collapse
Affiliation(s)
- Sayantap Datta
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
| | - Sindhura Pasham
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| | - Sriram Inavolu
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| | - Krishna M Boini
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
| | - Saisudha Koka
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| |
Collapse
|
|
10
|
Ali S, Zulfiqar M, Summer M, Arshad M, Noor S, Nazakat L, Javed A. Zebrafish as an innovative model for exploring cardiovascular disease induction mechanisms and novel therapeutic interventions: a molecular insight. Mol Biol Rep 2024; 51:904. [PMID: 39133413 DOI: 10.1007/s11033-024-09814-w] [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: 06/03/2024] [Accepted: 07/22/2024] [Indexed: 08/13/2024]
Abstract
Cardiovascular disease (CVD) is a common cardiac disorder that leads to heart attacks, strokes, and heart failure. It is primarily characterized by conditions that impact the heart and blood arteries, including peripheral artery disease, arrhythmias, atherosclerosis, myocardial ischemia, congenital heart abnormalities, heart failure, rheumatic heart disease, hypertension, and cardiomyopathies. These conditions are mainly effect the heart and blood vessels, causing blockages or weakened pumping, due to severe hereditary and environmental factors. The frequency of CVD is rising significantly as life expectancy increases. Despite this, no effective treatment or management for its symptoms has been found. One of the most difficult obstacles to overcome, is finding a suitable animal model for drug screening and drug development. Although rodents, mice, swine, and mammals serve as the basis for most animal models of cardiovascular disease, no model accurately captures the epidemiology of the condition. Zebrafish (Danio rerio) have drawn the interest of the international scientific community due to certain shortcomings of the previously discussed animal models because they are smaller, less costly, and have an incredibly high rate of reproduction. This review article emphasizes the significance of using zebrafish as an animal model to investigate the possible facets of cardiovascular disease. Moreover, the ultimate purpose of this review article is to establish the advantages of employing zebrafish over other animal models and to investigate the boundaries of using zebrafish to study human disease. Furthermore, the mechanisms of cardiovascular diseases induction in zebrafish were covered to improve understanding for readers. Finally, the analysis of cardiotoxicity using Zebra fish model, is also explained. In order to stop the health index from deteriorating, the current study also covers some innovative, effective, and relatively safer treatments for treatment and management of cardiotoxicity.
Collapse
Affiliation(s)
- Shaukat Ali
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan.
| | - Maryam Zulfiqar
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Muhammad Summer
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Mahnoor Arshad
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Shehzeen Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Laiba Nazakat
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Abdullah Javed
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| |
Collapse
|
|
11
|
Li M, Liu L, Zhang C, Deng L, Zhong Y, Liao B, Li X, Wan Y, Feng J. The latest emerging drugs for the treatment of diabetic cardiomyopathy. Expert Opin Pharmacother 2024; 25:641-654. [PMID: 38660817 DOI: 10.1080/14656566.2024.2347468] [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: 02/05/2024] [Accepted: 04/22/2024] [Indexed: 04/26/2024]
Abstract
INTRODUCTION Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus involving multiple pathophysiologic mechanisms. In addition to hypoglycemic agents commonly used in diabetes, metabolism-related drugs, natural plant extracts, melatonin, exosomes, and rennin-angiotensin-aldosterone system are cardioprotective in DCM. However, there is a lack of systematic summarization of drugs for DCM. AREAS COVERED In this review, the authors systematically summarize the most recent drugs used for the treatment of DCM and discusses them from the perspective of DCM pathophysiological mechanisms. EXPERT OPINION We discuss DCM drugs from the perspective of the pathophysiological mechanisms of DCM, mainly including inflammation and metabolism. As a disease with multiple pathophysiological mechanisms, the combination of drugs may be more advantageous, and we have discussed some of the current studies on the combination of drugs.
Collapse
Affiliation(s)
- Minghao Li
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Lin Liu
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Chunyu Zhang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Li Deng
- Department of Rheumatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yi Zhong
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| | - Bin Liao
- Department of Cardiovascular Surgery, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiuying Li
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University; Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
| | - Ying Wan
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University; Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, China
| | - Jian Feng
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
| |
Collapse
|
|
12
|
Tang J, Tam E, Song E, Xu A, Sweeney G. Crosstalk between myocardial autophagy and sterile inflammation in the development of heart failure. AUTOPHAGY REPORTS 2024; 3:2320605. [PMID: 40395524 PMCID: PMC11864620 DOI: 10.1080/27694127.2024.2320605] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 02/02/2024] [Accepted: 02/13/2024] [Indexed: 05/22/2025]
Abstract
Heart failure, a leading driver of global mortality, remains a topic of intense contemporary research interest due to the prevailing unmet need in cardiometabolic therapeutics. Numerous mechanisms with the potential to influence the onset and development of heart failure remain incompletely understood. Firstly, myocardial autophagy, which involves lysosomal degradation of damaged cellular components, confers context-dependent beneficial and detrimental effects. Secondly, sterile inflammation may arise following cardiac stress and exacerbate the progression of heart failure. Inflammation changes in a temporal manner and its onset must be adequately resolved to limit progression of heart failure. Mitochondria are an important factor in contributing to sterile inflammation by releasing damage associated molecular patterns (DAMPs) including mitochondrial DNA (mtDNA). Accordingly, this is one reason why the selective autophagy of mitochondria to maintain optimal function is important in determining cardiac function. In this review, we examine the increasing evidence suggesting crosstalk between autophagy and sterile inflammation together with their role in the development of heart failure. In particular, this is exemplified in the preclinical models of ischaemia/reperfusion injury and pressure overload induced heart failure. We also highlight potential therapeutic approaches focusing on autophagy and addressing sterile inflammation, aiming to enhance outcomes in heart failure.
Collapse
Affiliation(s)
- Jialing Tang
- Department of Biology, York University, Toronto, ON, Canada
| | - Eddie Tam
- Department of Biology, York University, Toronto, ON, Canada
| | - Erfei Song
- Department of Medicine, School of Clinical Medicine, State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Metabolic and Bariatric Surgery, the First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Aimin Xu
- Department of Medicine, School of Clinical Medicine, State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China
| | - Gary Sweeney
- Department of Biology, York University, Toronto, ON, Canada
| |
Collapse
|
|
13
|
Zhong C, Xie Y, Wang H, Chen W, Yang Z, Zhang L, Deng Q, Cheng T, Li M, Ju J, Liu Y, Liang H. Berberine inhibits NLRP3 inflammasome activation by regulating mTOR/mtROS axis to alleviate diabetic cardiomyopathy. Eur J Pharmacol 2024; 964:176253. [PMID: 38096968 DOI: 10.1016/j.ejphar.2023.176253] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 12/01/2023] [Accepted: 12/01/2023] [Indexed: 12/29/2023]
Abstract
Diabetes cardiomyopathy (DCM) refers to myocardial dysfunction and disorganization resulting from diabetes. In this study, we investigated the effects of berberine on cardiac function in male db/db mice with metformin as a positive control. After treatment for 8 weeks, significant improvements in cardiac function and a reduction in collagen deposition were observed in db/db mice. Furthermore, inflammation and pyroptosis were seen to decrease in these mice, as evidenced by decreased expressions of p-mTOR, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1β, IL-18, caspase-1, and gasdermin D (GSDMD). In vitro experiments on H9C2 cells showed that glucose exposure at 33 mmol/L induced pyroptosis, whereas berberine treatment reduced the expression of p-mTOR and NLRP3 inflammasome components. Moreover, berberine treatment was seen to inhibit the generation of mitochondrial reactive oxygen species (mtROS) and effectively improve cell damage in high glucose-induced H9C2 cells. The mTOR inhibitor, Torin-1, showed a therapeutic effect similar to that of berberine, by reducing the expression of NLRP3 inflammasome components and inhibiting mtROS generation. However, the activation of mTOR by MHY1485 partially nullified berberine's protective effects during high glucose stress. Collectively, our study reveals the mechanism that berberine regulates the mTOR/mtROS axis to inhibit pyroptosis induced by NLRP3 inflammasome activation, thereby alleviating DCM.
Collapse
Affiliation(s)
- Changsheng Zhong
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Yilin Xie
- School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518055, China
| | - Huifang Wang
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Wenxian Chen
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Zhenbo Yang
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Lei Zhang
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Qin Deng
- School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Guangdong, 518055, China
| | - Ting Cheng
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Mengyang Li
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China
| | - Jin Ju
- School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518055, China
| | - Yanyan Liu
- Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China.
| | - Haihai Liang
- Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
| |
Collapse
|
|
14
|
Wang G, Ma TY, Huang K, Zhong JH, Lu SJ, Li JJ. Role of pyroptosis in diabetic cardiomyopathy: an updated review. Front Endocrinol (Lausanne) 2024; 14:1322907. [PMID: 38250736 PMCID: PMC10796545 DOI: 10.3389/fendo.2023.1322907] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 12/06/2023] [Indexed: 01/23/2024] Open
Abstract
Diabetic cardiomyopathy (DCM), one of the common complications of diabetes, presents as a specific cardiomyopathy with anomalies in the structure and function of the heart. With the increasing prevalence of diabetes, DCM has a high morbidity and mortality worldwide. Recent studies have found that pyroptosis, as a programmed cell death accompanied by an inflammatory response, exacerbates the growth and genesis of DCM. These studies provide a theoretical basis for exploring the potential treatment of DCM. Therefore, this review aims to summarise the possible mechanisms by which pyroptosis promotes the development of DCM as well as the relevant studies targeting pyroptosis for the possible treatment of DCM, focusing on the molecular mechanisms of NLRP3 inflammasome-mediated pyroptosis, different cellular pyroptosis pathways associated with DCM, the effects of pyroptosis occurring in different cells on DCM, and the relevant drugs targeting NLRP3 inflammasome/pyroptosis for the treatment of DCM. This review might provide a fresh perspective and foundation for the development of therapeutic agents for DCM.
Collapse
Affiliation(s)
- Gan Wang
- Department of Cardiology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, China
| | - Tian-Yi Ma
- Department of Cardiology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, China
| | - Kang Huang
- Department of Cardiology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, China
| | - Jiang-Hua Zhong
- Department of Cardiology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, China
| | - Shi-Juan Lu
- Department of Cardiology, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, Hainan, 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, Beijing, China
| |
Collapse
|
|
15
|
Nițulescu IM, Ciulei G, Cozma A, Procopciuc LM, Orășan OH. From Innate Immunity to Metabolic Disorder: A Review of the NLRP3 Inflammasome in Diabetes Mellitus. J Clin Med 2023; 12:6022. [PMID: 37762961 PMCID: PMC10531881 DOI: 10.3390/jcm12186022] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 09/14/2023] [Accepted: 09/16/2023] [Indexed: 09/29/2023] Open
Abstract
The role of the NLRP3 inflammasome is pivotal in the pathophysiology and progression of diabetes mellitus (DM), encompassing both type 1 (T1D), or type 2 (T2D). As part of the innate immune system, NLRP3 is also responsible for the chronic inflammation triggered by hyperglycemia. In both conditions, NLRP3 facilitates the release of interleukin-1β and interleukin-18. For T1D, NLRP3 perpetuates the autoimmune cascade, leading to the destruction of pancreatic islet cells. In T2D, its activation is associated with the presence of insulin resistance. NLRP3 activation is also instrumental for the presence of numerous complications associated with DM, microvascular and macrovascular. A considerable number of anti-diabetic drugs have demonstrated the ability to inhibit the NLRP3 inflammasome.
Collapse
Affiliation(s)
- Iris Maria Nițulescu
- Department 4 of Internal Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (I.M.N.); (A.C.); (O.H.O.)
| | - George Ciulei
- Department 4 of Internal Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (I.M.N.); (A.C.); (O.H.O.)
| | - Angela Cozma
- Department 4 of Internal Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (I.M.N.); (A.C.); (O.H.O.)
| | - Lucia Maria Procopciuc
- Department 2 of Molecular Sciences, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Olga Hilda Orășan
- Department 4 of Internal Medicine, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (I.M.N.); (A.C.); (O.H.O.)
| |
Collapse
|
|
16
|
Hu Y, Zhang S, Lou H, Mikaye MS, Xu R, Meng Z, Du M, Tang P, Chen Z, Chen Y, Liu X, Du Z, Zhang Y. Aloe-Emodin Derivative, an Anthraquinone Compound, Attenuates Pyroptosis by Targeting NLRP3 Inflammasome in Diabetic Cardiomyopathy. Pharmaceuticals (Basel) 2023; 16:1275. [PMID: 37765083 PMCID: PMC10536457 DOI: 10.3390/ph16091275] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 08/27/2023] [Accepted: 09/06/2023] [Indexed: 09/29/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is widely recognized as a major contributing factor to the development of heart failure in patients with diabetes. Previous studies have demonstrated the potential benefits of traditional herbal medicine for alleviating the symptoms of cardiomyopathy. We have chemically designed and synthesized a novel compound called aloe-emodin derivative (AED), which belongs to the aloe-emodin (AE) family of compounds. AED was formed by covalent binding of monomethyl succinate to the anthraquinone mother nucleus of AE using chemical synthesis techniques. The purpose of this study was to investigate the effects and mechanisms of AED in treating DCM. We induced type 2 diabetes in Sprague-Dawley (SD) rats by administering a high-fat diet and streptozotocin (STZ) injections. The rats were randomly divided into six groups: control, DCM, AED low concentration (50 mg/kg/day), AED high concentration (100 mg/kg/day), AE (100 mg/kg/day), and positive control (glyburide, 2 mg/kg/day) groups. There were eight rats in each group. The rats that attained fasting blood glucose of ˃16.7 mmol/L were considered successful models. We observed significant improvements in cardiac function in the DCM rats with both AED and AE following four weeks of intragastric treatment. However, AED had a more pronounced therapeutic effect on DCM compared to AE. AED exhibited an inhibitory effect on the inflammatory response in the hearts of DCM rats and high-glucose-treated H9C2 cells by suppressing the pyroptosis pathway mediated by the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain 3 (NLRP3) inflammasome. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes showed a significant enrichment in the NOD-like receptor signaling pathway compared to the high-glucose group. Furthermore, overexpression of NLRP3 effectively reversed the anti-pyroptosis effects of AED in high-glucose-treated H9C2 cells. This study is the first to demonstrate that AED possesses the ability to inhibit myocardial pyroptosis in DCM. Targeting the pyroptosis pathway mediated by the NLRP3 inflammasome could provide a promising therapeutic strategy to enhance our understanding and treatment of DCM.
Collapse
Affiliation(s)
- Yingying Hu
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Shuqian Zhang
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Han Lou
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Monayo Seth Mikaye
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Run Xu
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Ziyu Meng
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Menghan Du
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Pingping Tang
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Zhouxiu Chen
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Yongchao Chen
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
| | - Xin Liu
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
- Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China
| | - Zhimin Du
- Institute of Clinical Pharmacology, The Second Affliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin 150086, China
- Department of Clinical Pharmacology College of Pharmacy, Harbin Medical University, Harbin 150081, China
- State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China
| | - Yong Zhang
- Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China
- Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China
- Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin 150086, China
| |
Collapse
|
|
17
|
Theofilis P, Oikonomou E, Chasikidis C, Tsioufis K, Tousoulis D. Inflammasomes in Atherosclerosis-From Pathophysiology to Treatment. Pharmaceuticals (Basel) 2023; 16:1211. [PMID: 37765019 PMCID: PMC10537692 DOI: 10.3390/ph16091211] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/20/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque accumulation, remains a significant global health challenge. In recent years, inflammasomes, the intracellular multiprotein complexes crucial for initiating innate immune responses, have emerged as key players in atherosclerosis pathophysiology. This review article aims to provide a comprehensive overview of the current understanding of inflammasome activation and its impact on atherosclerosis development and progression. We explore the intricate interplay between traditional cardiovascular risk factors and inflammasome activation, leading to the perpetuation of inflammatory cascades that drive plaque formation and instability. The review focuses on the molecular mechanisms underlying inflammasome activation, including the role of pattern recognition receptors and cytokines in this process. Moreover, we discuss the contribution of inflammasomes to endothelial dysfunction, foam cell formation, and vascular inflammation. Additionally, recent advances in therapeutic strategies targeting inflammasomes are examined, including pharmacological agents and potential immunomodulatory approaches. By collating and analyzing the current evidence, this review provides valuable insights into the potential of inflammasome-targeted therapies for atherosclerosis management and treatment. Understanding the pivotal role of inflammasomes in atherosclerosis pathophysiology offers promising prospects for developing effective and personalized therapeutic interventions that can mitigate the burden of this prevalent cardiovascular disorder and improve patient outcomes.
Collapse
Affiliation(s)
- Panagiotis Theofilis
- 1st Department of Cardiology, “Hippokration” General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.T.)
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, Thoracic Diseases General Hospital “Sotiria”, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Christos Chasikidis
- Department of Cardiology, General Hospital of Corinth, 20100 Corinth, Greece
| | - Konstantinos Tsioufis
- 1st Department of Cardiology, “Hippokration” General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.T.)
| | - Dimitris Tousoulis
- 1st Department of Cardiology, “Hippokration” General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.T.)
| |
Collapse
|
|
18
|
Saha S, Singh P, Dutta A, Vaidya H, Negi PC, Sengupta S, Seth S, Basak T. A Comprehensive Insight and Mechanistic Understanding of the Lipidomic Alterations Associated With DCM. JACC. ASIA 2023; 3:539-555. [PMID: 37614533 PMCID: PMC10442885 DOI: 10.1016/j.jacasi.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/17/2023] [Accepted: 06/03/2023] [Indexed: 08/25/2023]
Abstract
Dilated cardiomyopathy (DCM) is one of the major causes of heart failure characterized by the enlargement of the left ventricular cavity and contractile dysfunction of the myocardium. Lipids are the major sources of energy for the myocardium. Impairment of lipid homeostasis has a potential role in the pathogenesis of DCM. In this review, we have summarized the role of different lipids in the progression of DCM that can be considered as potential biomarkers. Further, we have also explained the mechanistic pathways followed by the lipid molecules in disease progression along with the cardioprotective role of certain lipids. As the global epidemiological status of DCM is alarming, it is high time to define some disease-specific biomarkers with greater prognostic value. We are proposing an adaptation of a system lipidomics-based approach to profile DCM patients in order to achieve a better diagnosis and prognosis of the disease.
Collapse
Affiliation(s)
- Shubham Saha
- School of Biosciences and Bioengineering. IIT-Mandi, Mandi, India
- BioX Center, Indian Institute of Technology-Mandi, Mandi, India
| | - Praveen Singh
- CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
| | - Abhi Dutta
- School of Biosciences and Bioengineering. IIT-Mandi, Mandi, India
- BioX Center, Indian Institute of Technology-Mandi, Mandi, India
| | - Hiteshi Vaidya
- Department of Cardiology, Indira Gandhi Medical College & Hospital, Shimla, India
| | - Prakash Chand Negi
- Department of Cardiology, Indira Gandhi Medical College & Hospital, Shimla, India
| | - Shantanu Sengupta
- CSIR-Institute of Genomics and Integrative Biology, New Delhi, India
| | - Sandeep Seth
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Trayambak Basak
- School of Biosciences and Bioengineering. IIT-Mandi, Mandi, India
- BioX Center, Indian Institute of Technology-Mandi, Mandi, India
| |
Collapse
|
|
19
|
Zivkovic S, Maric G, Cvetinovic N, Lepojevic-Stefanovic D, Bozic Cvijan B. Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review. Nutrients 2023; 15:nu15061517. [PMID: 36986246 PMCID: PMC10053759 DOI: 10.3390/nu15061517] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/15/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is directly correlated to the risk of CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority of these drugs, in addition to their lipid-lowering properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on the observation that a decrease in lipid levels occurs along with a decrease in inflammation. Insufficient reduction in the inflammation during treatment with lipid-lowering drugs could be one of the explanations for treatment failure and recurrent CVD events. Thus, the aim of this narrative review was to evaluate the anti-inflammatory properties of currently available lipid-lowering medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, and niacin, as well as dietary supplements and novel drugs used in modern times.
Collapse
Affiliation(s)
- Stefan Zivkovic
- Department of Cardiovascular Disease, Zvezdara University Medical Center, 11000 Belgrade, Serbia
| | - Gorica Maric
- Faculty of Medicine, Institute of Epidemiology, University of Belgrade, Dr. Subotica 8, 11000 Belgrade, Serbia
| | - Natasa Cvetinovic
- Department of Cardiovascular Disease, University Medical Center "Dr Dragisa Misovic-Dedinje", 11000 Belgrade, Serbia
| | | | - Bojana Bozic Cvijan
- Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| |
Collapse
|
|
20
|
Deng J, Yan F, Tian J, Qiao A, Yan D. Potential clinical biomarkers and perspectives in diabetic cardiomyopathy. Diabetol Metab Syndr 2023; 15:35. [PMID: 36871006 PMCID: PMC9985231 DOI: 10.1186/s13098-023-00998-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 02/15/2023] [Indexed: 03/06/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication and the leading cause of death in diabetic patients. Patients typically do not experience any symptoms and have normal systolic and diastolic cardiac functions in the early stages of DCM. Because the majority of cardiac tissue has already been destroyed by the time DCM is detected, research must be conducted on biomarkers for early DCM, early diagnosis of DCM patients, and early symptomatic management to minimize mortality rates among DCM patients. Most of the existing implemented clinical markers are not very specific for DCM, especially in the early stages of DCM. Recent studies have shown that a number of new novel markers, such as galactin-3 (Gal-3), adiponectin (APN), and irisin, have significant changes in the clinical course of the various stages of DCM, suggesting that we may have a positive effect on the identification of DCM. As a summary of the current state of knowledge regarding DCM biomarkers, this review aims to inspire new ideas for identifying clinical markers and related pathophysiologic mechanisms that could be used in the early diagnosis and treatment of DCM.
Collapse
Affiliation(s)
- Jianxin Deng
- Department of Endocrinology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen Clinical Research Center for Metabolic Diseases, No. 3002, Sungang West Road, Futian District, Shenzhen, 518035, Guangdong Province, China
| | - Fang Yan
- Geriatric Diseases Institute of Chengdu, Center for Medicine Research and Translation, Chengdu Fifth People's Hospital, Chengdu, 611137, Sichuan Province, China
| | - Jinglun Tian
- Department of Geriatrics, the Traditional Chinese Medicine Hospital of Wenjiang District, Chengdu, 611130, China
| | - Aijun Qiao
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528400, Guangdong Province, China.
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
| | - Dewen Yan
- Department of Endocrinology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen Clinical Research Center for Metabolic Diseases, No. 3002, Sungang West Road, Futian District, Shenzhen, 518035, Guangdong Province, China.
| |
Collapse
|
|
21
|
Zhao Z, Wang X, Lu M, Gao Y. Rosuvastatin Improves Endothelial Dysfunction in Diabetes by Normalizing Endoplasmic Reticulum Stress via Calpain-1 Inhibition. Curr Pharm Des 2023; 29:2579-2590. [PMID: 37881071 DOI: 10.2174/0113816128250494231016065438] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 07/06/2023] [Accepted: 08/31/2023] [Indexed: 10/27/2023]
Abstract
BACKGROUND Rosuvastatin contributes to the improvement of vascular complications in diabetes, but the protective mechanisms remain unclear. The aim of the present study was to investigate the effect and mechanism of rosuvastatin on endothelial dysfunction induced by diabetes. METHODS Calpain-1 knockout (Capn1 EK684-/-) and C57BL/6 mice were intraperitoneally injected with STZ to induce type 1 diabetes. Human umbilical vein endothelial cells (HUVECs) were incubated with high glucose in this study. The function of isolated vascular rings, apoptosis, and endoplasmic reticulum stress (ERS) indicators were measured in this experiment. RESULTS The results showed that rosuvastatin (5 mg/kg/d) and calpain-1 knockout improved impaired vasodilation in an endothelial-dependent manner, and this effect was abolished by an ERS inducer. Rosuvastatin administration inhibited calpain-1 activation and ERS induced by high glucose, as well as apoptosis and oxidative stress both in vivo and in vitro. In addition, an ERS inducer (tunicamycin) offset the beneficial effect of rosuvastatin on endothelial dysfunction and ERS, which was accompanied by increased calpain-1 expression. The ERS inhibitor showed a similar improvement in endothelial dysfunction with rosuvastatin but could not increase the improvement in endothelial function of rosuvastatin. CONCLUSION These results suggested that rosuvastatin improves endothelial dysfunction by suppressing calpain- 1 and normalizing ERS, subsequently decreasing apoptosis and oxidative stress.
Collapse
Affiliation(s)
- Zhao Zhao
- Cardiovascular Department, Tianjin Medical University General Hospital, Tianjin, China
- The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Xinpeng Wang
- The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Meili Lu
- Liaoning Provincial Key Laboratory of Cardiovascular Drugs, Jinzhou Medical University, Jinzhou, China
| | - Yuxia Gao
- Cardiovascular Department, Tianjin Medical University General Hospital, Tianjin, China
| |
Collapse
|
|
22
|
Patil P, Doshi G. Deciphering the Role of Pyroptosis Impact on Cardiovascular Diseases. Curr Drug Targets 2023; 24:1166-1183. [PMID: 38164730 DOI: 10.2174/0113894501267496231102114410] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 01/03/2024]
Abstract
Pyroptosis has become a noteworthy area of focus in recent years due to its association with inflammatory diseases. Pyroptosis is a type of programmed cell death accompanied by an inflammatory response, and the discovery of the gasdermin family has expanded the study of pyroptosis. The primary characteristics of pyroptosis include cell expansion, membrane penetration, and the ejection of cell contents. In healthy physiology, pyroptosis is an essential part of the host's defence against pathogen infection. Excessive Pyroptosis, however, can lead to unchecked and persistent inflammatory responses, including the emergence of inflammatory diseases. More precisely, gasdermin family members have a role in the creation of membrane holes during pyroptosis, which leads to cell lysis. It is also related to how pro-inflammatory intracellular substances, including IL-1, IL-18, and High mobility group box 1 (HMGB1), are used. Two different signalling pathways, one of which is regulated by caspase-1 and the other by caspase-4/5/11, are the primary causes of pyroptosis. Cardiovascular diseases are often associated with cell death and acute or chronic inflammation, making this area of research particularly relevant. In this review, we first systematically summarize recent findings related to Pyroptosis, exploring its characteristics and the signalling pathway mechanisms, as well as various treatment strategies based on its modulation that has emerged from the studies. Some of these strategies are currently undergoing clinical trials. Additionally, the article elaborates on the scientific evidence indicating the role of Pyroptosis in various cardiovascular diseases. As a whole, this should shed insight into future paths and present innovative ideas for employing Pyroptosis as a strong disease-fighting weapon.
Collapse
Affiliation(s)
- Poonam Patil
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, VLM Road, Vile Parle (w), Mumbai, 400056, India
| | - Gaurav Doshi
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, VLM Road, Vile Parle (w), Mumbai, 400056, India
| |
Collapse
|
|
23
|
Zhu N, Huang B, Zhu L. Bibliometric analysis of the inflammation in diabetic cardiomyopathy. Front Cardiovasc Med 2022; 9:1006213. [PMID: 36582738 PMCID: PMC9792483 DOI: 10.3389/fcvm.2022.1006213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 11/18/2022] [Indexed: 12/15/2022] Open
Abstract
Background Maladaptive inflammation is implicated in the development of diabetic cardiomyopathy (DCM). This study aimed to visually analyze the global scientific output over the past two decades regarding research on inflammation associated with DCM. Methods All relevant articles and reviews were retrieved in the Web of Science (WOS) Core Collection (limited to SCIE) using "inflammation" and "diabetic cardiomyopathy" as search terms. Articles and reviews published from 1 January 2001 to 28 February 2021 were collected. Visualization analysis and statistical analysis were conducted by Microsoft 365 Excel and VOSviewer 1.6.18. Results A total of 578 documents were finally selected for further analysis. The publications regarding inflammation and DCM increased gradually over approximately 20 years. The most prolific country was China, with 296 documents and the most citations (9,366). The most influential author groups were Lu Cai and Yihui Tan who were from the United States. The bibliometric analysis of co-occurrence keywords showed that inflammation in DCM is composed of numerous molecules (NF-κB, NLRP3 inflammasome, Nrf-2, TNF-α, protein kinase C, PPARα, TLR4, p38 mitogen-activated protein kinase, TGF-β, Sirt1, and AKT), a variety of cardiac cell types (stem cell, fibroblast, and cardiomyocyte), physiological processes (apoptosis, oxidative stress, autophagy, endoplasmic reticulum stress, hypertrophy, mitochondrion dysfunction, and proliferation), and drugs (sulforaphane, metformin, empagliflozin, and rosuvastatin). Conclusion Our bibliometric analysis presents the characteristics and trends of inflammation in DCM and shows that research on inflammation in DCM will continue to be a hotspot.
Collapse
Affiliation(s)
- Ning Zhu
- Department of Cardiology, The Third Affiliated Hospital of Shanghai University, Wenzhou People’s Hospital, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China,*Correspondence: Ning Zhu,
| | - Bingwu Huang
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
| | - Liuyan Zhu
- Department of General Practice, The Third Affiliated Hospital of Shanghai University, Wenzhou People’s Hospital, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
|
24
|
The Role of NLRP3 Inflammasome in Diabetic Cardiomyopathy and Its Therapeutic Implications. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3790721. [PMID: 36111168 PMCID: PMC9470324 DOI: 10.1155/2022/3790721] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022]
Abstract
Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM). However, the precise molecular mechanisms remain largely unclear, and it is still a challenging disease to diagnose and treat. The nucleotide-binding oligomerization domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome is a critical part of the innate immune system in the host to defend against endogenous danger and pathogenic microbial infections. Dysregulated NLRP3 inflammasome activation results in the overproduction of cytokines, primarily IL-1β and IL-18, and eventually, inflammatory cell death-pyroptosis. A series of studies have indicated that NLRP3 inflammasome activation participates in the development of DCM, and that corresponding interventions could mitigate disease progression. Accordingly, this narrative review is aimed at briefly summarizing the cell-specific role of the NLRP3 inflammasome in DCM and provides novel insights into developing DCM therapeutic strategies targeting the NLRP3 inflammasome.
Collapse
|
|
25
|
Fu F, Doroudgar S. IRE1/XBP1 and endoplasmic reticulum signaling - from basic to translational research for cardiovascular disease. CURRENT OPINION IN PHYSIOLOGY 2022; 28:100552. [PMID: 37207249 PMCID: PMC10195104 DOI: 10.1016/j.cophys.2022.100552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Most cellular protein synthesis, including synthesis of membrane-targeted and secreted proteins, which are critical for cellular and organ crosstalk, takes place at the endoplasmic reticulum (ER), placing the ER at the nexus of cellular signaling, growth, metabolism, and stress sensing. Ample evidence has established the dysregulation of protein homeostasis and the ER unfolded protein response (UPR) in cardiovascular disease. However, the mechanisms of stress sensing and signaling in the ER are incompletely defined. Recent studies have defined notable functions for the inositol-requiring kinase 1 (IRE1)/X-box- binding protein-1 (XBP1) branch of the UPR in regulation of cardiac function. This review highlights the mechanisms underlying IRE1 activation and the IRE1 interactome, which reveals unexpected functions for the UPR and summarizes our current understanding of the functions of IRE1 in cardiovascular disease.
Collapse
Affiliation(s)
- Fangyi Fu
- Department of Cardiology, Angiology, and Pneumology, Heidelberg University Hospital, Heidelberg, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany
| | - Shirin Doroudgar
- Department of Internal Medicine and the Translational Cardiovascular Research Center, University of Arizona - College of Medicine - Phoenix, Phoenix, AZ, United States
| |
Collapse
|
|
26
|
Fan J, Ren M, Adhikari BK, Wang H, He Y. The NLRP3 Inflammasome as a Novel Therapeutic Target for Cardiac Fibrosis. J Inflamm Res 2022; 15:3847-3858. [PMID: 35836721 PMCID: PMC9273832 DOI: 10.2147/jir.s370483] [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: 04/12/2022] [Accepted: 07/01/2022] [Indexed: 11/23/2022] Open
Abstract
Cardiac fibrosis often has adverse cardiovascular effects, including heart failure, sudden death, and malignant arrhythmias. However, there is no targeted therapy for cardiac fibrosis. Inflammation is known to play a crucial role in the disorder, and the NLR pyrin domain-containing-3 (NLRP3) inflammasome is closely associated with innate immunity. Therefore, further understanding the pathophysiological role of the inflammasome in cardiac fibrosis may provide novel strategies for the prevention and treatment of the disorder. The aim of this review was to summarize the present knowledge of NLRP3 inflammasome-related mechanisms underlying cardiac fibrosis and to suggest potential targeted therapy that could be used to treat the condition.
Collapse
Affiliation(s)
- Jiwen Fan
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China
| | - Meng Ren
- Department of Medical Oncology, Jilin Provincial Cancer Hospital, Changchun, People's Republic of China
| | - Binay Kumar Adhikari
- Department of Cardiology, Nepal Armed Police Force (APF) Hospital, Kathmandu, Nepal
| | - Haodong Wang
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China
| | - Yuquan He
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China
| |
Collapse
|
|
27
|
Zhou C, Yin X. Wogonin Ameliorated Obesity-Induced Lipid Metabolism Disorders and Cardiac Injury via Suppressing Pyroptosis and Deactivating IL-17 Signaling Pathway. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 50:1553-1564. [PMID: 35770725 DOI: 10.1142/s0192415x22500653] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Obesity leads to structural and functional changes in the heart and has become a global burden of disease. Wogonin is a natural flavonoid which possesses cardioprotective, neuroprotective, and anti-cancer properties. However, the effects of wogonin on obesity-induced cardiac injury remain unclear. In this study, the high-fat diet (HFD)-induced obese mice model was successfully established. Moreover, HFD induced a fat mass and cardiac injury in mice. More importantly, wogonin treatment reduced fat mass and improved cardiac function of HFD mice. Consistently, wogonin ameliorated myocardial lipid metabolism in HFD-induced obese mice by reducing triglyceride (TC), total cholesterol (TG), and non-esterified fatty acid (NEFA) levels in serum, as well as the TG and free fatty acids (FFA) levels in heart tissues. Interestingly, wogonin treatment alleviated myocardial pyroptosis in HFD-induced obese mice. Through bioinformatic analysis, the IL-17 signaling pathway was predicted to be modulated by wogonin. Results showed that wogonin deactivated the IL-17 signaling pathway in HFD mice. These findings suggested that wogonin ameliorated obesity-induced disorders of lipid metabolism and cardiac injury via suppressing pyroptosis and deactivating the IL-17 signaling pathway, which provided a novel therapeutic strategy for HFD-induced cardiac injury.
Collapse
Affiliation(s)
- Cheng Zhou
- Department of Paediatrics, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213164, P. R. China
| | - Xiaoling Yin
- Department of Paediatrics, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, Jiangsu 213164, P. R. China
| |
Collapse
|
|
28
|
Elia E, Ministrini S, Carbone F, Montecucco F. Diabetic cardiomyopathy and inflammation: development of hostile microenvironment resulting in cardiac damage. Minerva Cardiol Angiol 2022; 70:357-369. [PMID: 33427423 DOI: 10.23736/s2724-5683.20.05454-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Diabetes mellitus is emerging as a major risk factor for heart failure. Diabetic cardiomyopathy is defined as a myocardial dysfunction that is not caused by underlying hypertension or coronary artery disease. Studies about clinical features, natural history and outcomes of the disease are few and often conflicting, because a universally accepted operative definition of diabetic cardiomyopathy is still lacking. Hyperglycemia and related metabolic and endocrine disorders are the triggering factors of myocardial damage in diabetic cardiomyopathy through multiple mechanisms. Among these mechanisms, inflammation has a relevant role, similar to other chronic myocardial disease, such as hypertensive or ischemic heart disease. A balance between inflammatory damage and healing processes is fundamental for homeostasis of myocardial tissue, whereas diabetes mellitus produces an imbalance, promoting inflammation and delaying healing. Therefore, diabetes-related chronic inflammatory state can produce a progressive qualitative deterioration of myocardial tissue, which reflects on progressive left ventricular functional impairment, which can be either diastolic, with prevalent myocardial hypertrophy, or systolic, with prevalent myocardial fibrosis. The aim of this narrative review is to summarize the existing evidence about the role of inflammation in diabetic cardiomyopathy onset and development. Ultimately, potential pharmacological strategies targeting inflammatory response will be reviewed and discussed.
Collapse
Affiliation(s)
- Edoardo Elia
- Division of Cardiology, Department of Internal Medicine, Città della Salute e della Scienza, Turin, Italy
| | - Stefano Ministrini
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy -
- IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy
| |
Collapse
|
|
29
|
García-Fernández-Bravo I, Torres-Do-Rego A, López-Farré A, Galeano-Valle F, Demelo-Rodriguez P, Alvarez-Sala-Walther LA. Undertreatment or Overtreatment With Statins: Where Are We? Front Cardiovasc Med 2022; 9:808712. [PMID: 35571155 PMCID: PMC9105719 DOI: 10.3389/fcvm.2022.808712] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/29/2022] [Indexed: 12/26/2022] Open
Abstract
Statins, in addition to healthy lifestyle interventions, are the cornerstone of lipid-lowering therapy. Other low-density lipoprotein (LDL)-lowering drugs include ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. As new evidence emerges from new clinical trials, therapeutic goals change, leading to renewed clinical guidelines. Nowadays, LDL goals are getting lower, leading to the "lower is better" paradigm in LDL-cholesterol (LDL-C) management. Several observational studies have shown that LDL-C control in real life is suboptimal in both primary and secondary preventions. It is critical to enhance the adherence to guideline recommendations through shared decision-making between clinicians and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities. This narrative review summarizes the evidence regarding the benefits of lipid-lowering drugs in reducing cardiovascular events, the pleiotropic effect of statins, real-world data on overtreatment and undertreatment of lipid-lowering therapies, and the changing LDL-C in targets in the clinical guidelines of dyslipidemias over the years.
Collapse
Affiliation(s)
| | - Ana Torres-Do-Rego
- Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Grupo (departamento) de investigación Riesgo cardiovascular y lípidos, Instituto de investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Antonio López-Farré
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Francisco Galeano-Valle
- Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Grupo (departamento) de investigación Riesgo cardiovascular y lípidos, Instituto de investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Pablo Demelo-Rodriguez
- Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Grupo (departamento) de investigación Riesgo cardiovascular y lípidos, Instituto de investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Luis A. Alvarez-Sala-Walther
- Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Grupo (departamento) de investigación Riesgo cardiovascular y lípidos, Instituto de investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| |
Collapse
|
|
30
|
Yu Q, Guo M, Zeng W, Zeng M, Zhang X, Zhang Y, Zhang W, Jiang X, Yu B. Interactions between NLRP3 inflammasome and glycolysis in macrophages: New insights into chronic inflammation pathogenesis. Immun Inflamm Dis 2022; 10:e581. [PMID: 34904398 PMCID: PMC8926505 DOI: 10.1002/iid3.581] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 12/11/2022] Open
Abstract
NLRP3 inflammasome activation in macrophages fuels sterile inflammation, which has been tied with metabolic reprogramming characterized by high glycolysis and low oxidative phosphorylation. The key enzymes in glycolysis and glycolysis‐related products can regulate and activate NLRP3 inflammasome. In turn, NLRP3 inflammasome is considered to affect glycolysis, as well. However, the exact mechanism remains ambiguous. On the basis of these findings, the focus of this review is mainly on the developments in our understanding of interaction between NLRP3 inflammasome activation and glycolysis in macrophages, and small molecule compounds that influence the activation of NLRP3 inflammasomes by regulating glycolysis in macrophages. The application of this interaction in the treatment of diseases is also discussed. This paper may yield valuable clues for development of novel therapeutic agent for NLRP3 inflammasome‐related diseases.
Collapse
Affiliation(s)
- Qun Yu
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Maojuan Guo
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wenyun Zeng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Miao Zeng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaolu Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yue Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wenlan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xijuan Jiang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Bin Yu
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| |
Collapse
|
|
31
|
Longo M, Scappaticcio L, Cirillo P, Maio A, Carotenuto R, Maiorino MI, Bellastella G, Esposito K. Glycemic Control and the Heart: The Tale of Diabetic Cardiomyopathy Continues. Biomolecules 2022; 12:biom12020272. [PMID: 35204778 PMCID: PMC8961546 DOI: 10.3390/biom12020272] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/25/2022] [Accepted: 02/01/2022] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular diseases are the leading cause of death in people with diabetes. Diabetic cardiomyopathy (DC) is an important complication of diabetes and represents a distinct subtype of heart failure that occurs in absence of cardiovascular diseases. Chronic hyperglycemia and hyperinsulinemia along with insulin resistance and inflammatory milieu are the main mechanisms involved in the pathophysiology of DC. Changes in lifestyle favoring healthy dietary patterns and physical activity, combined with more innovative anti-diabetes therapies, are the current treatment strategies to safeguard the cardiovascular system. This review aims at providing an updated comprehensive overview of clinical, pathogenetic, and molecular aspects of DC, with a focus on the effects of anti-hyperglycemic drugs on the prevention of pump dysfunction and consequently on cardiovascular health in type 2 diabetes.
Collapse
Affiliation(s)
- Miriam Longo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
- Division of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Lorenzo Scappaticcio
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
| | - Paolo Cirillo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
| | - Antonietta Maio
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
| | - Raffaela Carotenuto
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
- Division of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Maria Ida Maiorino
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
- Division of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Giuseppe Bellastella
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
- Division of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Katherine Esposito
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.L.); (L.S.); (P.C.); (A.M.); (R.C.); (M.I.M.); (G.B.)
- Division of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- Correspondence: ; Tel.: +39-08-156-65031
| |
Collapse
|
|
32
|
Sun X, Sun X, Meng H, Wu J, Guo X, Du L, Wu H. Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy. Nutrients 2022; 14:nu14020368. [PMID: 35057549 PMCID: PMC8780413 DOI: 10.3390/nu14020368] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/09/2022] [Accepted: 01/09/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM), resulting in high mortality. Myocardial fibrosis, cardiomyocyte apoptosis and inflammatory cell infiltration are hallmarks of DCM, leading to cardiac dysfunction. To date, few effective approaches have been developed for the intervention of DCM. In the present study, we investigate the effect of krill oil (KO) on the prevention of DCM using a mouse model of DM induced by streptozotocin and a high-fat diet. The diabetic mice developed pathological features, including cardiac fibrosis, apoptosis and inflammatory cell infiltration, the effects of which were remarkably prevented by KO. Mechanistically, KO reversed the DM-induced cardiac expression of profibrotic and proinflammatory genes and attenuated DM-enhanced cardiac oxidative stress. Notably, KO exhibited a potent inhibitory effect on NLR family pyrin domain containing 3 (NLRP3) inflammasome that plays an important role in DCM. Further investigation showed that KO significantly upregulated the expression of Sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which are negative regulators of NLRP3. The present study reports for the first time the preventive effect of KO on the pathological injuries of DCM, providing SIRT3, PGC-1α and NLRP3 as molecular targets of KO. This work suggests that KO supplementation may be a viable approach in clinical prevention of DCM.
Collapse
Affiliation(s)
- Xuechun Sun
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China; (X.S.); (H.M.); (X.G.)
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China
| | - Xiaodan Sun
- Intensive Care Unit, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Rd., Jinan 250033, China;
| | - Huali Meng
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China; (X.S.); (H.M.); (X.G.)
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China
| | - Junduo Wu
- Department of Cardiology, The Second Hospital of Jilin University, 218 Ziqiang St., Changchun 130041, China;
| | - Xin Guo
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China; (X.S.); (H.M.); (X.G.)
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China
| | - Lei Du
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China; (X.S.); (H.M.); (X.G.)
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China
- Correspondence: (L.D.); (H.W.)
| | - Hao Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Rd., Jinan 250012, China; (X.S.); (H.M.); (X.G.)
- Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, 105 Jiefang Rd., Jinan 250013, China
- Correspondence: (L.D.); (H.W.)
| |
Collapse
|
|
33
|
Muñoz-Córdova F, Hernández-Fuentes C, Lopez-Crisosto C, Troncoso MF, Calle X, Guerrero-Moncayo A, Gabrielli L, Chiong M, Castro PF, Lavandero S. Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies. Front Cardiovasc Med 2022; 8:707336. [PMID: 35004869 PMCID: PMC8734937 DOI: 10.3389/fcvm.2021.707336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 11/29/2021] [Indexed: 12/17/2022] Open
Abstract
Diabetic cardiomyopathy (DCM) is a severe complication of diabetes developed mainly in poorly controlled patients. In DCM, several clinical manifestations as well as cellular and molecular mechanisms contribute to its phenotype. The production of reactive oxygen species (ROS), chronic low-grade inflammation, mitochondrial dysfunction, autophagic flux inhibition, altered metabolism, dysfunctional insulin signaling, cardiomyocyte hypertrophy, cardiac fibrosis, and increased myocardial cell death are described as the cardinal features involved in the genesis and development of DCM. However, many of these features can be associated with broader cellular processes such as inflammatory signaling, mitochondrial alterations, and autophagic flux inhibition. In this review, these mechanisms are critically discussed, highlighting the latest evidence and their contribution to the pathogenesis of DCM and their potential as pharmacological targets.
Collapse
Affiliation(s)
- Felipe Muñoz-Córdova
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile
| | - Carolina Hernández-Fuentes
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile
| | - Camila Lopez-Crisosto
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile.,Division of Cardiovascular Diseases, Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), Pontifical Catholic University of Chile, Santiago, Chile
| | - Mayarling F Troncoso
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile.,Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Ximena Calle
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile
| | - Alejandra Guerrero-Moncayo
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile
| | - Luigi Gabrielli
- Division of Cardiovascular Diseases, Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), Pontifical Catholic University of Chile, Santiago, Chile
| | - Mario Chiong
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile
| | - Pablo F Castro
- Division of Cardiovascular Diseases, Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), Pontifical Catholic University of Chile, Santiago, Chile.,Corporación Centro de Estudios Científicos de las Enfermedades Crónicas (CECEC), University of Chile, Santiago, Chile
| | - Sergio Lavandero
- Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santiago, Chile.,Corporación Centro de Estudios Científicos de las Enfermedades Crónicas (CECEC), University of Chile, Santiago, Chile.,Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, United States
| |
Collapse
|
|
34
|
Atorvastatin suppresses NLRP3 inflammasome activation in intracerebral hemorrhage via TLR4- and MyD88-dependent pathways. Aging (Albany NY) 2022; 14:462-476. [PMID: 35017318 PMCID: PMC8791214 DOI: 10.18632/aging.203824] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/28/2021] [Indexed: 11/25/2022]
Abstract
Intracerebral hemorrhage (ICH) is a common neurological condition that causes severe disability and even death. Even though the mechanism is not clear, increasing evidence shows the efficacy of atorvastatin on treating ICH. In this study, we examined the impact of atorvastatin on the NOD-like receptor protein 3 (NLRP3) inflammasome and inflammatory pathways following ICH. Mouse models of ICH were established by collagenase injection in adult C57BL/6 mice. IHC mice received atorvastatin treatment 2 h after hematoma establishment. First, the changes of glial cells and neurons in the brains of ICH patients and mice were detected by immunohistochemistry and western blotting. Second, the molecular mechanisms underlying the microglial activation and neuronal loss were evaluated after the application of atorvastatin. Finally, the behavioral deficits of ICH mice without or with the treatment of atorvastatin were determined by neurological defect scores. The results demonstrated that atorvastatin significantly deactivated glial cells by reducing the expression of glial fibrillary acidic protein (GFAP), Ionized calcium binding adapter molecule 1 (Iba1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in ICH model mice. For inflammasomes, atorvastatin also showed its efficacy by decreasing the expression of NLRP3, cleaved caspase-1, and IL-1β in ICH mice. Moreover, atorvastatin markedly inhibited the upregulation of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88), which indicated deactivation of NLRP3 inflammasomes. By inhibiting the activities of inflammasomes in glial cells, neuronal loss was partially prevented by suppressing the apoptosis in the brains of ICH mice, protecting them from neurological defects.
Collapse
|
|
35
|
NLRP3 Inflammasome in Diabetic Cardiomyopathy and Exercise Intervention. Int J Mol Sci 2021; 22:ijms222413228. [PMID: 34948026 PMCID: PMC8707657 DOI: 10.3390/ijms222413228] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/24/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetic cardiomyopathy (DCM), as a common complication of diabetes, is characterized by chronic low-grade inflammation. The NLRP3 inflammasome is a key sensor mediating innate immune and inflammatory responses. However, the mechanisms initiating and promoting NLRP3 inflammasome activation in DCM is largely unexplored. The aim of the present review is to describe the link between NLRP3 inflammasome and DCM, and to provide evidence highlighting the importance of exercise training in DCM intervention. Collectively, this evidence suggests that DCM is an inflammatory disease aggravated by NLRP3 inflammasome-mediated release of IL-1β and IL-18. In addition, chronic exercise intervention is an effective preventive and therapeutic method to alleviate DCM via modulating the NLRP3 inflammasome.
Collapse
|
|
36
|
Molecular mechanism and therapeutic targeting of necrosis, apoptosis, pyroptosis, and autophagy in cardiovascular disease. Chin Med J (Engl) 2021; 134:2647-2655. [PMID: 34608069 PMCID: PMC8631411 DOI: 10.1097/cm9.0000000000001772] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
ABSTRACT Cell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis.
Collapse
|
|
37
|
Peng M, Liu Y, Xu Y, Li L, Li Y, Yang H. Cathelicidin-WA ameliorates diabetic cardiomyopathy by inhibiting the NLRP3 inflammasome. Cell Cycle 2021; 20:2278-2290. [PMID: 34585633 DOI: 10.1080/15384101.2021.1981631] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Cathelicidin-WA (CWA) is a novel cathelicidin peptide isolated from snakes that has been suggested to exert anti-inflammatory effects. The aim of our study was to investigate whether cathelicidin-WA (CWA) could protect the heart from diabetic cardiomyopathy (DCM). Streptozotocin (STZ) injection was used to establish a mouse model of DCM. CWA peptide (2 mg/kg or 8 mg/kg) was continuously administered to the mice from 10 weeks to 16 weeks after STZ injection. The mice in the DCM group exhibited cardiac dysfunction, while 8 mg/kg CWA ameliorated this cardiac dysfunction. Cardiac fibrosis, inflammation, and oxidative stress as well as cardiomyocyte apoptosis in the DCM mice were decreased by treatment with 8 mg/kg CWA. We isolated neonatal rat cardiomyocytes and stimulated the cells with high glucose to establish an in vitro model of myocyte cell injury. Consistently, CWA inhibited high glucose-induced cell death, inflammation and oxidative stress in the myocytes. Moreover, CWA reduced the formation of the NLR family pyrin domain-containing 3 (NRLP3) inflammasome by regulating thioredoxin-interacting protein expression and p65 activation. NLRP3 overexpression inhibited the beneficial effects of CWA on the heart during DCM and on high glucose-induced myocyte injury. In summary, CWA attenuates cardiac injury and preserves cardiac function during DCM by targeting the NLRP3 pathway.Abbreviations: AAV9: Adeno associated virus; AGE: Advanced Glycation End products; CWA: Cathelicidin-WA; DCM: diabetic cardiomyopathy; Gpx: glutathione peroxidase; HG: high glucose; IL: Interleukin; NLR: Family Pyrin Domain Containing 3 (NRLP3); TXNIP: Thioredoxin interacting protein; LVEF: left ventricular ejection fraction; MDA: Malondialdehyde; MnSOD: manganese superoxide dismutase; NADPH: Nicotinamide adenine dinucleotide phosphate; NAC: N-acetyl-cysteine; NRCMs: Neonatal rat cardiomyocytes; ROS: reactive oxygen species; STZ: Streptozotocin; TNFa: tumor necrosis factor a.
Collapse
Affiliation(s)
- Meng Peng
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuan Liu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yawei Xu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li Li
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Li
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haibo Yang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
38
|
Mamun AA, Wu Y, Nasrin F, Akter A, Taniya MA, Munir F, Jia C, Xiao J. Role of Pyroptosis in Diabetes and Its Therapeutic Implications. J Inflamm Res 2021; 14:2187-2206. [PMID: 34079327 PMCID: PMC8164340 DOI: 10.2147/jir.s291453] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/14/2021] [Indexed: 12/13/2022] Open
Abstract
Pyroptosis is mainly considered as a new pro-inflammatory mediated-programmed cell death. In addition, pyroptosis is described by gasdermin-induced pore formation on the membrane, cell swelling and rapid lysis, and several pro-inflammatory mediators interleukin-1β (IL-1β) and interleukin-18 (IL-18) release. Extensive studies have shown that pyroptosis is commonly involved by activating the caspase-1-dependent canonical pathway and caspase-4/5/11-dependent non-canonical pathway. However, pyroptosis facilitates local inflammation and inflammatory responses. Current researches have reported that pyroptosis promotes the progression of several diabetic complications. Emerging studies have suggested that some potential molecules targeting the pyroptosis and inflammasome signaling pathways could be a novel therapeutic avenue for managing and treating diabetes and its complications in the near future. Our narrative review concisely describes the possible mechanism of pyroptosis and its progressive understanding of the development of diabetic complications.
Collapse
Affiliation(s)
- Abdullah Al Mamun
- Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou, Zhejiang Province, 325035, People's Republic of China
| | - Yanqing Wu
- Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang Province, 325035, People's Republic of China
| | - Fatema Nasrin
- Institute of Health and Biomedical Innovation, Translational Research Institute, Brisbane, Australia.,School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia
| | - Afroza Akter
- Department of Microbiology, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Masuma Afrin Taniya
- Department of Life Sciences, School of Environment and Life Sciences, Independent University, Bangladesh, Dhaka, 1229, Bangladesh
| | - Fahad Munir
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People's Republic of China
| | - Chang Jia
- Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China
| | - Jian Xiao
- Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital and School of Pharmaceutical Sciences, Wenzhou, Zhejiang Province, 325035, People's Republic of China
| |
Collapse
|
|
39
|
Gedefaw L, Ullah S, Leung PHM, Cai Y, Yip SP, Huang CL. Inflammasome Activation-Induced Hypercoagulopathy: Impact on Cardiovascular Dysfunction Triggered in COVID-19 Patients. Cells 2021; 10:916. [PMID: 33923537 PMCID: PMC8073302 DOI: 10.3390/cells10040916] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/09/2021] [Accepted: 04/14/2021] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is the most devastating infectious disease in the 21st century with more than 2 million lives lost in less than a year. The activation of inflammasome in the host infected by SARS-CoV-2 is highly related to cytokine storm and hypercoagulopathy, which significantly contribute to the poor prognosis of COVID-19 patients. Even though many studies have shown the host defense mechanism induced by inflammasome against various viral infections, mechanistic interactions leading to downstream cellular responses and pathogenesis in COVID-19 remain unclear. The SARS-CoV-2 infection has been associated with numerous cardiovascular disorders including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The inflammatory response triggered by the activation of NLRP3 inflammasome under certain cardiovascular conditions resulted in hyperinflammation or the modulation of angiotensin-converting enzyme 2 signaling pathways. Perturbations of several target cells and tissues have been described in inflammasome activation, including pneumocytes, macrophages, endothelial cells, and dendritic cells. The interplay between inflammasome activation and hypercoagulopathy in COVID-19 patients is an emerging area to be further addressed. Targeted therapeutics to suppress inflammasome activation may have a positive effect on the reduction of hyperinflammation-induced hypercoagulopathy and cardiovascular disorders occurring as COVID-19 complications.
Collapse
Affiliation(s)
| | | | | | | | - Shea-Ping Yip
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China; (L.G.); (S.U.); (P.H.M.L.); (Y.C.)
| | - Chien-Ling Huang
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China; (L.G.); (S.U.); (P.H.M.L.); (Y.C.)
| |
Collapse
|
|
40
|
Lv S, Li X, Wang H. The Role of the Effects of Endoplasmic Reticulum Stress on NLRP3 Inflammasome in Diabetes. Front Cell Dev Biol 2021; 9:663528. [PMID: 33937267 PMCID: PMC8079978 DOI: 10.3389/fcell.2021.663528] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Endoplasmic reticulum (ER) is an important organelle for the protein synthesis, modification, folding, assembly, and the transport of new peptide chains. When the folding ability of ER proteins is impaired, the accumulation of unfolded or misfolded proteins in ER leads to endoplasmic reticulum stress (ERS). The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, can induce the maturation and secretion of interleukin-1beta (IL-1β) and IL-18 through activating caspase-1. It is associated with many diseases. Studies have shown that ERS can regulate NLRP3 inflammasome in many diseases including diabetes. However, the mechanism of the effects of ERS on NLRP3 inflammasome in diabetes has not been fully understood. This review summarizes the recent researches about the effects of ERS on NLRP3 inflammasome and the related mechanism in diabetes to provide ideas for the relevant basic research in the future.
Collapse
Affiliation(s)
- Shuangyu Lv
- Bioinformatics Center, School of Basic Medical Sciences, Institute of Biomedical Informatics, Henan University, Kaifeng, China
| | - Xiaotian Li
- Bioinformatics Center, School of Basic Medical Sciences, Institute of Biomedical Informatics, Henan University, Kaifeng, China
| | - Honggang Wang
- Bioinformatics Center, School of Basic Medical Sciences, Institute of Biomedical Informatics, Henan University, Kaifeng, China
| |
Collapse
|
|
41
|
Koushki K, Shahbaz SK, Mashayekhi K, Sadeghi M, Zayeri ZD, Taba MY, Banach M, Al-Rasadi K, Johnston TP, Sahebkar A. Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways. Clin Rev Allergy Immunol 2021; 60:175-199. [PMID: 32378144 PMCID: PMC7985098 DOI: 10.1007/s12016-020-08791-9] [Citation(s) in RCA: 224] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Atherosclerosis is one type of cardiovascular disease (CVD) in which activation of the NLRP3 inflammasome and toll-like receptor (TLR) pathways is implicated. One of the most effective treatments for atherosclerosis is the use of statin medications. Recent studies have indicated that statins, in addition to their lipid-lowering effects, exert inhibitory and/or stimulatory effects on the NLRP3 inflammasome and TLRs. Some of the statins lead to activation of the inflammasome and subsequently cause secretion of IL-1β and IL-18. Thus, these actions may further aggravate the disease. On the other hand, some statins cause inhibition of the inflammasome or TLRs and along with lipid-lowering, help to improve the disease by reducing inflammation. In this article, we discuss these contradictory studies and the mechanisms of action of statins on the NLRP3 inflammasome and TLR pathways. The dose-dependent effects of statins on the NLRP3 complex are related to their chemistry, pharmacokinetic properties, and danger signals. Lipophilic statins have more pleiotropic effects on the NLRP3 complex in comparison to hydrophilic statins. Statins can suppress TLR4/MyD88/NF-ĸB signaling and cause an immune response shift to an anti-inflammatory response. Furthermore, statins inhibit the NF-ĸB pathway by decreasing the expression of TLRs 2 and 4. Statins are cost-effective drugs, which should have a continued future in the treatment of atherosclerosis due to both their immune-modulating and lipid-lowering effects.
Collapse
Affiliation(s)
- Khadijeh Koushki
- Department of Immunology, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sanaz Keshavarz Shahbaz
- Department of Immunology, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kazem Mashayekhi
- Department of Immunology, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahvash Sadeghi
- Department of Immunology, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zeinab Deris Zayeri
- Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Maciej Banach
- Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland
- Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Khalid Al-Rasadi
- Medical Research Centre, Sultan Qaboos University, Muscat, Oman
- Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Amirhossein Sahebkar
- Halal Research Center of IRI, FDA, Tehran, Iran.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
42
|
Dulka K, Szabo M, Lajkó N, Belecz I, Hoyk Z, Gulya K. Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains. Int J Mol Sci 2021; 22:ijms22073412. [PMID: 33810299 PMCID: PMC8059142 DOI: 10.3390/ijms22073412] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 03/17/2021] [Accepted: 03/24/2021] [Indexed: 12/16/2022] Open
Abstract
Rosuvastatin (RST) is primarily used to treat high cholesterol levels. As it has potentially harmful but not well-documented effects on embryos, RST is contraindicated during pregnancy. To demonstrate whether RST could induce molecular epigenetic events in the brains of newborn rats, pregnant mothers were treated daily with oral RST from the 11th day of pregnancy for 10 days (or until delivery). On postnatal day 1, the brains of the control and RST-treated rats were removed for Western blot or immunohistochemical analyses. Several antibodies that recognize different methylation sites for H2A, H2B, H3, and H4 histones were quantified. Analyses of cell-type-specific markers in the newborn brains demonstrated that prenatal RST administration did not affect the composition and cell type ratios as compared to the controls. Prenatal RST administration did, however, induce a general, nonsignificant increase in H2AK118me1, H2BK5me1, H3, H3K9me3, H3K27me3, H3K36me2, H4, H4K20me2, and H4K20me3 levels, compared to the controls. Moreover, significant changes were detected in the number of H3K4me1 and H3K4me3 sites (134.3% ± 19.2% and 127.8% ± 8.5% of the controls, respectively), which are generally recognized as transcriptional activators. Fluorescent/confocal immunohistochemistry for cell-type-specific markers and histone methylation marks on tissue sections indicated that most of the increase at these sites belonged to neuronal cell nuclei. Thus, prenatal RST treatment induces epigenetic changes that could affect neuronal differentiation and development.
Collapse
Affiliation(s)
- Karolina Dulka
- Department of Cell Biology and Molecular Medicine, University of Szeged, 6720 Szeged, Hungary; (K.D.); (M.S.); (N.L.)
| | - Melinda Szabo
- Department of Cell Biology and Molecular Medicine, University of Szeged, 6720 Szeged, Hungary; (K.D.); (M.S.); (N.L.)
| | - Noémi Lajkó
- Department of Cell Biology and Molecular Medicine, University of Szeged, 6720 Szeged, Hungary; (K.D.); (M.S.); (N.L.)
| | - István Belecz
- Department of Medical Biology, University of Szeged, 6720 Szeged, Hungary;
| | - Zsófia Hoyk
- Biological Barriers Research Group, Institute of Biophysics, Biological Research Center, Eötvös Loránd Research Network, 6726 Szeged, Hungary;
| | - Karoly Gulya
- Department of Cell Biology and Molecular Medicine, University of Szeged, 6720 Szeged, Hungary; (K.D.); (M.S.); (N.L.)
- Correspondence:
| |
Collapse
|
|
43
|
Abstract
Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.
Collapse
Affiliation(s)
- Wang-Soo Lee
- Division of Cardiology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Corresponding authors: Wang-Soo Lee https://orcid.org/0000-0002-8264-0866 Division of Cardiology, Department of Internal Medicine, Chung-Ang University Hospital, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea E-mail:
| | - Jaetaek Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
- Corresponding authors: Wang-Soo Lee https://orcid.org/0000-0002-8264-0866 Division of Cardiology, Department of Internal Medicine, Chung-Ang University Hospital, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea E-mail:
| |
Collapse
|
|
44
|
Taohuajing reduces oxidative stress and inflammation in diabetic cardiomyopathy through the sirtuin 1/nucleotide-binding oligomerization domain-like receptor protein 3 pathway. BMC Complement Med Ther 2021; 21:78. [PMID: 33637069 PMCID: PMC7913206 DOI: 10.1186/s12906-021-03218-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 01/13/2021] [Indexed: 12/11/2022] Open
Abstract
Background Oxidative stress and inflammation promote the development of diabetic cardiomyopathy (DCM). Therefore, inhibiting these processes may show beneficial effects in the treatment of patients with DCM. Taohuajing (THJ) is prepared using Persicae semen (Taoren), Polygonatum sibiricum (Huangjing), and Carthami flos (Honghua) and may have applications in the treatment of DCM. However, the protective effects of THJ have not been thoroughly assessed. Accordingly, in this study, we aimed to investigate the protective effects of THJ in a model of DCM and further clarify the potential mechanisms. Methods A type 2 diabetes mellitus model was generated using male C57BL/6 mice. Echocardiography and histopathology were used to evaluate cardiac function. The expression levels of cytokines were measured using enzyme-linked immunosorbent assays. Western blotting and small interfering RNA were used to evaluate the targets of THJ. Results Compared with the control group, DCM mice showed cardiac dysfunction, metabolic disorder, fibrosis, and disorganized ultrastructure, and THJ treatment significantly inhibited these changes significantly. THJ treatment also inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), induced the production of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), decreased the levels of pro-inflammatory cytokines, and suppressed the activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. These protective effects were abolished by sirtinol, an inhibitor of sirtuin1 (SIRT1). Conclusions Overall, THJ protected the heart from hyperglycemia-induced oxidative stress and inflammation in DCM mice via a mechanism involving SIRT1-mediated antioxidant proteins and suppression of the NLRP3 inflammasome.
Collapse
|
|
45
|
Jia W, Bai T, Zeng J, Niu Z, Fan D, Xu X, Luo M, Wang P, Zou Q, Dai X. Combined Administration of Metformin and Atorvastatin Attenuates Diabetic Cardiomyopathy by Inhibiting Inflammation, Apoptosis, and Oxidative Stress in Type 2 Diabetic Mice. Front Cell Dev Biol 2021; 9:634900. [PMID: 33718370 PMCID: PMC7945946 DOI: 10.3389/fcell.2021.634900] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 01/12/2021] [Indexed: 12/19/2022] Open
Abstract
Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus, may eventually leads to irreversible heart failure. Metformin is the cornerstone of diabetes therapy, especially for type 2 diabetes. Statins are widely used to reduce the risk of cardiovascular diseases. In this study, we aimed to investigate whether the combined administration of metformin and atorvastatin could achieve superior protective effects on DCM and to elucidate its molecular mechanism. Here, db/db mice (9–10 weeks old) were randomly divided into four groups, including sterile water group (DM), metformin group (MET, 200 mg/kg/day), atorvastatin group (AVS, 10 mg/kg/day), and combination therapy group (MET + AVS). Mice were treated with different drugs via gavage once per day for 3 months. After 3 months of treatment, the pathological changes (inflammation, fibrosis, hypertrophy, and oxidative stress makers) were detected by histopathological techniques, as well as Western blotting. The H9C2 cardiomyocytes were treated with palmitate (PAL) to mimic diabetic condition. The cells were divided into control group, PAL treatment group, MET + PAL treatment group, AVS + PAL treatment group, and MET + AVS + PAL treatment group. The effects of MET and AVS on the cell viability and inflammation of H9C2 cells subjected to PAL condition were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. Both MET and AVS prevented diabetes-induced fibrosis, hypertrophy, and inflammation. The combination therapy showed superior effects in protecting myocardial tissue against diabetes-induced injury. Mechanistically, the combination therapy significantly inhibited oxidative stress and the expression levels of inflammation-related proteins, e.g., NLRP3, caspase-1, interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), and P-p65/p65, in both cardiac tissues and H9C2 cells. TUNEL assay showed that the combination therapy significantly attenuated the apoptosis of cardiomyocytes; decreased the expression level of pro-apoptotic-related proteins, such as cleaved caspase-3 and BAX; and enhanced the expression level of anti-apoptotic protein (Bcl-2). Furthermore, the combination therapy remarkably upregulated the expression levels of 5′-AMP-activated protein kinase (AMPK) and SIRT1. Our findings indicated that the anti-inflammation and anti-apoptosis effects of the combination therapy may be related to activation of AMPK/SIRT1 signaling pathway.
Collapse
Affiliation(s)
- Weikun Jia
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Tao Bai
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, China
| | - Jiang Zeng
- School of Basic Medicine, Chengdu Medical College, Chengdu, China
| | - Zijing Niu
- School of Biosciences and Technology, Chengdu Medical College, Chengdu, China
| | - Daogui Fan
- School of Biosciences and Technology, Chengdu Medical College, Chengdu, China
| | - Xin Xu
- School of Basic Medicine, Chengdu Medical College, Chengdu, China
| | - Meiling Luo
- School of Biosciences and Technology, Chengdu Medical College, Chengdu, China
| | - Peijian Wang
- Department of Cardiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Qingliang Zou
- Department of Cardiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xiaozhen Dai
- School of Biosciences and Technology, Chengdu Medical College, Chengdu, China
| |
Collapse
|
|
46
|
Wu A, Sun W, Mou F. lncRNA‑MALAT1 promotes high glucose‑induced H9C2 cardiomyocyte pyroptosis by downregulating miR‑141‑3p expression. Mol Med Rep 2021; 23:259. [PMID: 33576445 PMCID: PMC7893681 DOI: 10.3892/mmr.2021.11898] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Accepted: 12/03/2020] [Indexed: 01/21/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is caused by diabetes and can result in heart failure. Long non-coding RNAs (lncRNAs) have been demonstrated to be closely associated with DCM development. The present study aimed to investigate whether lncRNA-metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) altered high glucose (HG)-induced H9C2 cardiomyocyte pyroptosis by targeting microRNA (miR)-141-3p. H9C2 cells were treated with normal glucose (NG) or HG. lncRNA-MALAT1 and miR-141-3p expression levels were determined via reverse transcription-quantitative PCR (RT-qPCR). MALAT1 and miR-141-3p knockdown and overexpression were established and confirmed via RT-qPCR. The association between MALAT1 expression and miR-141-3p expression, as well as the induction of pyroptosis and gasdermin D (GSDMD)-N expression were evaluated by performing dual luciferase reporter, TUNEL staining and immunofluorescence staining assays, respectively. Western blotting was conducted to measure the expression levels of pyroptosis-associated proteins, including apoptosis-associated speck-like protein, GSDMD-N, caspase-1, nucleotide oligomerization domain-like receptor protein 3 and GSDMD. MALAT1 mRNA expression levels were significantly increased, whereas miR-141-3p expression levels were significantly decreased in HG-treated H9C2 cells compared with the NG group. Compared with the HG group, MALAT1 overexpression significantly reduced miR-141-3p expression levels, increased the rate of TUNEL positive cells and upregulated the expression levels of pyroptosis-associated proteins. MALAT1 knockdown displayed the opposite effect on the rate of TUNEL positive cells and the expression levels of pyroptosis-associated proteins. Furthermore, the rate of TUNEL positive cells, and GSDMD-N and pyroptosis-associated protein expression levels were significantly reduced by miR-141-3p overexpression in MALAT1-overexpression H9C2 cells. The results indicated that compared with NG treatment, HG treatment increased MALAT1 expression levels and decreased miR-141-3p expression levels in H9C2 cells. Therefore, the present study suggested that lncRNA-MALAT1 targeted miR-141-3p to promote HG-induced H9C2 cardiomyocyte pyroptosis.
Collapse
Affiliation(s)
- Aishan Wu
- Department of Cardiology II, Weihai Municipal Hospital, Weihai, Shandong 264200, P.R. China
| | - Weili Sun
- Department of Anesthesiology, Weihai Municipal Hospital, Weihai, Shandong 264200, P.R. China
| | - Fengying Mou
- Department of Ultrasound, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
| |
Collapse
|
|
47
|
Li F, Xu D, Hou K, Gou X, Lv N, Fang W, Li Y. Pretreatment of Indobufen and Aspirin and their Combinations with Clopidogrel or Ticagrelor Alleviates Inflammasome Mediated Pyroptosis Via Inhibiting NF-κB/NLRP3 Pathway in Ischemic Stroke. J Neuroimmune Pharmacol 2021; 16:835-853. [DOI: 10.1007/s11481-020-09978-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 12/17/2020] [Indexed: 12/17/2022]
|
|
48
|
Pellegrini C, Martelli A, Antonioli L, Fornai M, Blandizzi C, Calderone V. NLRP3 inflammasome in cardiovascular diseases: Pathophysiological and pharmacological implications. Med Res Rev 2021; 41:1890-1926. [PMID: 33460162 DOI: 10.1002/med.21781] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 11/30/2020] [Accepted: 12/15/2020] [Indexed: 12/11/2022]
Abstract
Growing evidence points out the importance of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome in the pathogenesis of cardiovascular diseases (CVDs), including hypertension, myocardial infarct (MI), ischemia, cardiomyopathies (CMs), heart failure (HF), and atherosclerosis. In this regard, intensive research efforts both in humans and in animal models of CVDs are being focused on the characterization of the pathophysiological role of NLRP3 inflammasome signaling in CVDs. In addition, clinical and preclinical evidence is coming to light that the pharmacological blockade of NLRP3 pathways with drugs, including novel chemical entities as well as drugs currently employed in the clinical practice, biologics and phytochemicals, could represent a suitable therapeutic approach for prevention and management of CVDs. On these bases, the present review article provides a comprehensive overview of clinical and preclinical studies about the role of NLRP3 inflammasome in the pathophysiology of CVDs, including hypertension, MI, ischemic injury, CMs, HF and atherosclerosis. In addition, particular attention has been focused on current evidence on the effects of drugs, biologics, and phytochemicals, targeting different steps of inflammasome signaling, in CVDs.
Collapse
Affiliation(s)
| | - Alma Martelli
- Department of Pharmacy, University of Pisa, Pisa, Italy
| | - Luca Antonioli
- Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy
| | - Matteo Fornai
- Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy
| | - Corrado Blandizzi
- Department of Clinical and Experimental Medicine, Unit of Pharmacology and Pharmacovigilance, University of Pisa, Pisa, Italy
| | | |
Collapse
|
|
49
|
Xie X, Bai G, Liu H, Zhang L, He Y, Qiang D, Zou X. Early Predictors in the Onset of Type 2 Diabetes at Different Fasting Blood Glucose Levels. Diabetes Metab Syndr Obes 2021; 14:1485-1492. [PMID: 33833539 PMCID: PMC8020326 DOI: 10.2147/dmso.s301352] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 03/12/2021] [Indexed: 12/26/2022] Open
Abstract
PURPOSE This study investigates the possible roles and potential prediction ability of metabolic parameters in the early development of T2D by detecting their serum levels at different fasting blood glucose (FBG) levels. METHODS The subjects were included and divided into normal glucose tolerance (NGT), prediabetes (PD), and T2Dsubgroups. Apart from detecting the levels of routine biochemical parameters, fasting serum insulin (FINS), 25(OH)D, thioredoxin-interacting protein (TXNIP), thioredoxin (TRX), and NOD-like receptor family, pyrin domain-containing 3 (NLRP3) were detected. β-cell dysfunction (HOMA-β) and insulin resistance (HOMA-IR) were assessed by homeostasis model assessment. Both univariate and multivariate logistic regression analyses were used to estimate the risk of metabolic parameters, and their optimal cut-off values were obtained in the receiver operating characteristic (ROC) curve analysis and the Youden index. RESULTS Among the 207 subjects, aged from 20 to 60 years (44.62+12.92) contain 118 males and 89 females. There was a significantly lower trend of TRX, HOMA-β, and 25(OH)D following the higher FBG level among these three subgroups, while a significantly higher trend of all the other metabolic parameters. The multivariate analysis showed that subjects with higher values of TRX, HOMA-β, and 25(OH)D had a significantly lower risk for patients to be diagnosed as PD (aOR: 0.945, 0.961, and 0.543) and T2D (aOR: 0.912, 0.947, 0.434). Under the reliable 95% CI, TXNIP with a cut-off value of 119.27 showed the highest AUC value, sensitivity, and specificity (AUC: 0.981, 95% CI: 0.8524-0.9839, 91.49%, and 83.33%) to diagnose PD. FINS with a cut-off value of 28.1 also showed the highest ones (AUC=0.9872, 95% CI: 0.9753-0.9992, 100%, and 92.91%) to diagnose T2D. CONCLUSION Early prediction of T2D is vital for timely intervention. Based on the FBG ≥100.8 mg/dl, the results provide evidence that 25(OH)D might be the protective factor in the early development of T2D. Besides, TXNIP and FINS might be the predictor for PD and T2D, respectively.
Collapse
Affiliation(s)
- Xiaomin Xie
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
- Correspondence: Xiaomin Xie Department of Endocrinology, The First People’s Hospital of Yinchuan, 2 Liqun Street, Xingqing District, Yinchuan, 750001, Ningxia, People’s Republic of ChinaTel +86 13895189599 Email
| | - Guirong Bai
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
| | - Huili Liu
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
| | - Li Zhang
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
| | - YanTing He
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
| | - Dan Qiang
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
| | - Xiaoyan Zou
- Department of Endocrinology, The First People’s Hospital of Yinchuan, Yinchuan, 750001, People’s Republic of China
| |
Collapse
|
|
50
|
Tong M, Ren K, Chen L, Zhao GJ. Statin ameliorates adipose inflammation via NLRP3 suppression. Int J Cardiol 2020; 301:154. [PMID: 31948593 DOI: 10.1016/j.ijcard.2019.10.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 10/08/2019] [Indexed: 10/25/2022]
Affiliation(s)
- Min Tong
- The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People's Hospital, Qingyuan, 511518, Guangdong, China; Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Kun Ren
- Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Lu Chen
- Department of Pathophysiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Guo-Jun Zhao
- The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People's Hospital, Qingyuan, 511518, Guangdong, China.
| |
Collapse
|