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Rafaqat S, Azam A, Hafeez R, Faseeh H, Tariq M, Asif M, Arshad A, Noshair I. Role of interleukins in the pathogenesis of coronary heart disease: A literature review. World J Cardiol 2025; 17:103947. [DOI: 10.4330/wjc.v17.i3.103947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/22/2025] [Accepted: 02/10/2025] [Indexed: 03/21/2025] Open
Abstract
Interleukins (ILs), a subset of cytokines, play a critical role in the pathogenesis of coronary heart disease (CHD) by mediating inflammation. This review article summarizes the role of ILs such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in the pathogenesis of CHD. Individuals with mild coronary artery disease (CAD) and angina who have ischemic heart disease have higher serum concentrations of IL-1b. Larger studies are needed to verify the safety and assess the effectiveness of low-dose IL-2 as an anti-inflammatory treatment. IL-3 is found more often in patients receiving coronary angioplasty compared to patients with asymptomatic CAD or without CAD. Serum levels of IL-4 are reliable indicators of CAD. An independent correlation between IL-5 and the incidence of CAD was demonstrated. IL-6 helps serve as a reliable biomarker for the degree of CAD, as determined by the Gensini score, and is a key factor in the development of atherosclerosis. Also, variants of IL-7/7R have been linked to the Han Chinese population's genetic susceptibility to CHD. IL-8 plays a role in the progression of CAD occurrences. By interacting with conventional risk factors for CAD, IL-9 may contribute to the development of CAD and offer an innovative approach to its prevention and management. There was a 34% increased risk of a CHD incident for every standard deviation rise in baseline IL-10 levels.
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Affiliation(s)
- Saira Rafaqat
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Azeem Azam
- Institute of Zoology, University of the Punjab, Lahore 54000, Pakistan
| | - Ramsha Hafeez
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Hamza Faseeh
- Department of Zoology, Govt. Islamia Graduate College Civil Lines, Lahore 54000, Pakistan
| | - Maria Tariq
- Department of Zoology, University of Education, Lahore 54000, Pakistan
| | - Muhammad Asif
- Department of Zoology, University of Education, Lahore 54000, Pakistan
| | - Amber Arshad
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
| | - Iqra Noshair
- Department of Zoology (Molecular Physiology), Lahore College for Women University, Lahore 54000, Pakistan
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Sidorkiewicz M. The Cardioprotective Effects of Polyunsaturated Fatty Acids Depends on the Balance Between Their Anti- and Pro-Oxidative Properties. Nutrients 2024; 16:3937. [PMID: 39599723 PMCID: PMC11597422 DOI: 10.3390/nu16223937] [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: 10/16/2024] [Revised: 11/08/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Polyunsaturated fatty acids (PUFAs) are not only structural components of membrane phospholipids and energy storage molecules in cells. PUFAs are important factors that regulate various biological functions, including inflammation, oxidation, and immunity. Both n-3 and n-6 PUFAs from cell membranes can be metabolized into pro-inflammatory and anti-inflammatory metabolites that, in turn, influence cardiovascular health in humans. The role that PUFAs play in organisms depends primarily on their structure, quantity, and the availability of enzymes responsible for their metabolism. n-3 PUFAs, such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), are generally known for anti-inflammatory and atheroprotective properties. On the other hand, n-6 FAs, such as arachidonic acid (AA), are precursors of lipid mediators that display mostly pro-inflammatory properties and may attenuate the efficacy of n-3 by competition for the same enzymes. However, a completely different light on the role of PUFAs was shed due to studies on the influence of PUFAs on new-onset atrial fibrillation. This review analyzes the role of PUFAs and PUFA derivatives in health-related effects, considering both confirmed benefits and newly arising controversies.
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Affiliation(s)
- Malgorzata Sidorkiewicz
- Department of Medical Biochemistry, Faculty of Health Sciences, Medical University of Lodz, 90-419 Lodz, Poland
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3
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Wang E, Fang C, Zhang J, Wang Y. Association between dietary inflammatory index and all-cause mortality risk in adults with coronary heart disease in the United States. Sci Rep 2024; 14:23998. [PMID: 39402099 PMCID: PMC11473697 DOI: 10.1038/s41598-024-75381-6] [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: 07/17/2024] [Accepted: 10/04/2024] [Indexed: 10/17/2024] Open
Abstract
Diet and inflammation are crucial in the incidence and progression of coronary heart disease (CHD). This study aimed to investigate the correlation between the Dietary inflammatory index (DII) and all-cause mortality in CHD patients. A total of 1,303 CHD patients from the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018 were included. Multivariate Cox regression was used to explore the correlation between the DII and the risk of all-cause mortality in these patients. Restricted cubic spline (RCS) analysis was also utilized to examine the relationship between the DII and all-cause mortality risk in CHD patients. Additionally, subgroup analyses were conducted to determine how the correlation between the DII and all-cause mortality varied across different demographics. During a median follow-up period of 77 months among 1,303 CHD patients, 536 died from all causes. The DII scores were significantly higher in deceased patients compared to survivors. After adjusting for confounding factors, the multivariate Cox regression analysis indicated a strong positive correlation between the DII and all-cause mortality in CHD patients. RCS analysis suggested a non-linear relationship between the DII and all-cause mortality among CHD patients. Additionally, an increase in DII was more pronounced in its impact on female patients. The DII is strongly correlated with the risk of all-cause mortality among CHD patients, particularly among females. Thus, managing dietary inflammation is vital for the prevention and treatment of CHD, especially in female patients.
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Affiliation(s)
- Enyang Wang
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230000, Anhui, China.
| | - Caoyang Fang
- Department of Emergency, First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei, 230000, Anhui, China
| | - Jing Zhang
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230000, Anhui, China
| | - Yuqi Wang
- Department of Cardiology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230000, Anhui, China
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Fularski P, Czarnik W, Dąbek B, Lisińska W, Radzioch E, Witkowska A, Młynarska E, Rysz J, Franczyk B. Broader Perspective on Atherosclerosis-Selected Risk Factors, Biomarkers, and Therapeutic Approach. Int J Mol Sci 2024; 25:5212. [PMID: 38791250 PMCID: PMC11121693 DOI: 10.3390/ijms25105212] [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: 03/30/2024] [Revised: 05/01/2024] [Accepted: 05/07/2024] [Indexed: 05/26/2024] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) stands as the leading cause of mortality worldwide. At its core lies a progressive process of atherosclerosis, influenced by multiple factors. Among them, lifestyle-related factors are highlighted, with inadequate diet being one of the foremost, alongside factors such as cigarette smoking, low physical activity, and sleep deprivation. Another substantial group of risk factors comprises comorbidities. Amongst others, conditions such as hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), or familial hypercholesterolemia (FH) are included here. Extremely significant in the context of halting progression is counteracting the mentioned risk factors, including through treatment of the underlying disease. What is more, in recent years, there has been increasing attention paid to perceiving atherosclerosis as an inflammation-related disease. Consequently, efforts are directed towards exploring new anti-inflammatory medications to limit ASCVD progression. Simultaneously, research is underway to identify biomarkers capable of providing insights into the ongoing process of atherosclerotic plaque formation. The aim of this study is to provide a broader perspective on ASCVD, particularly focusing on its characteristics, traditional and novel treatment methods, and biomarkers that can facilitate its early detection.
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Affiliation(s)
- Piotr Fularski
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Witold Czarnik
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Bartłomiej Dąbek
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Wiktoria Lisińska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewa Radzioch
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Alicja Witkowska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, ul. Zeromskiego 113, 90-549 Lodz, Poland
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de Liyis BG, Jagannatha GNP, Kosasih AM, Darma IKSS, Artha IMJR. Efficacy of single high-dose statin prior to percutaneous coronary intervention in acute coronary syndrome: a systematic review and meta-analysis. Egypt Heart J 2024; 76:49. [PMID: 38630377 PMCID: PMC11024076 DOI: 10.1186/s43044-024-00481-7] [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: 01/17/2024] [Accepted: 04/09/2024] [Indexed: 04/20/2024] Open
Abstract
BACKGROUND The impacts of single high-dose statin preloading in patients undergoing percutaneous coronary intervention (PCI) have not been fully examined. This study aims to evaluate post-procedure impacts of single high-dose statin pretreatment with acute coronary syndrome (ACS). METHODS The meta-analysis reviewed Cochrane, PubMed, and Medline databases for studies comparing single high-dose atorvastatin or rosuvastatin to placebo in ACS patients undergoing PCI. The primary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, and target vessel revascularization (TVR) at three months. Secondary endpoints examined were the TIMI flow grade 3 and left ventricular ejection fraction (LVEF). RESULTS Comprehensive analysis was conducted on fifteen RCTs, encompassing a total of 6,207 patients (3090 vs 3117 patients). The pooled results demonstrated that a single high-dose of statin administered prior to PCI led to a significant decrease in the incidence of MACE at three months post-PCI compared to the control group (OR 0.50, 95%CI 0.35-0.71, p = 0.0001). The occurrence of MI (OR 0.57, 95%CI 0.42-0.77, p = 0.0002), all-cause mortality (OR 0.56, 95%CI 0.39-0.81, p = 0.0002), and TVR (OR 0.56, 95%CI 0.35-0.92, p = 0.02) was significantly lower in the statin single high-dose group compared to the control group. No significant effects on TIMI flow grade 3 (OR 1.20, 95%CI 0.94-1.53, p = 0.14) or left ventricular ejection fraction (OR 2.19, 95%CI - 0.97 to 5.34, p = 0.17) were observed. Subgroup analysis demonstrated reduced incidence of MACE with a single dose of 80 mg atorvastatin (OR 0.66, 95%CI 0.54-0.81, p < 0.0001) and 40 mg rosuvastatin (OR 0.19, 95%CI 0.07-0.54, p = 0.002). CONCLUSIONS Single high-dose statin before PCI in patients with ACS significantly reduces MACE, MI, all-cause mortality, and TVR three months post-PCI.
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Affiliation(s)
- Bryan Gervais de Liyis
- Faculty of Medicine, Universitas Udayana, Prof. I.G.N.G Ngoerah General Hospital, Diponegoro Street, Denpasar, Bali, 80114, Indonesia.
| | - Gusti Ngurah Prana Jagannatha
- Faculty of Medicine, Universitas Udayana, Prof. I.G.N.G Ngoerah General Hospital, Diponegoro Street, Denpasar, Bali, 80114, Indonesia
| | - Anastasya Maria Kosasih
- Faculty of Medicine, Universitas Udayana, Prof. I.G.N.G Ngoerah General Hospital, Diponegoro Street, Denpasar, Bali, 80114, Indonesia
| | - I Kadek Susila Surya Darma
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Udayana, Prof. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
| | - I Made Junior Rina Artha
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Udayana, Prof. I.G.N.G Ngoerah General Hospital, Denpasar, Bali, Indonesia
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Ding P, Song Y, Yang Y, Zeng C. NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention. Front Pharmacol 2024; 15:1368835. [PMID: 38681198 PMCID: PMC11045953 DOI: 10.3389/fphar.2024.1368835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/02/2024] [Indexed: 05/01/2024] Open
Abstract
NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing protein complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 inflammasome leads to the production of pro-inflammatory cellular contents, such as interleukin (IL)-1β and IL-18, and induction of inflammatory cell death known as pyroptosis, thereby amplifying or sustaining inflammation. While a balanced inflammatory response is beneficial for resolving damage and promoting tissue healing, excessive activation of the NLRP3 inflammasome and pyroptosis can have harmful effects. The involvement of the NLRP3 inflammasome has been observed in various cardiovascular diseases (CVD). Indeed, the NLRP3 inflammasome and its associated pyroptosis are closely linked to key cardiovascular risk factors including hyperlipidemia, diabetes, hypertension, obesity, and hyperhomocysteinemia. Exercise compared with medicine is a highly effective measure for both preventing and treating CVD. Interestingly, emerging evidence suggests that exercise improves CVD and inhibits the activity of NLRP3 inflammasome and pyroptosis. In this review, the activation mechanisms of the NLRP3 inflammasome and its pathogenic role in CVD are critically discussed. Importantly, the purpose is to emphasize the crucial role of exercise in managing CVD by suppressing NLRP3 inflammasome activity and proposes it as the foundation for developing novel treatment strategies.
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Affiliation(s)
- Ping Ding
- Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yuanming Song
- Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yang Yang
- Zhuhai People’s Hospital, Zhuhai Clinical Medical College of Jinan University, Zhuhai, China
| | - Cheng Zeng
- Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, China
- Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China
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Hu J, Teng B, Xu Z, Wan Y, Jin G. A porous form Coomassie brilliant blue G250-isorhamnetin fluorescent composite coated with acrylic resin for tumor cell imaging. Front Chem 2023; 11:1260533. [PMID: 37789965 PMCID: PMC10544906 DOI: 10.3389/fchem.2023.1260533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 09/01/2023] [Indexed: 10/05/2023] Open
Abstract
Four distinct fluorescence complexes, the fluorescent complex-1 (FC-1), fluorescent complex-2 (FC-2), fluorescent complex third (FC-3) and fluorescent complex fourth (FC-4), were created using isorhamnetin and Coomassie brilliant blue G250 as raw materials. The issue of isorhamnetin's low solubility has been resolved, and isorhamnetin-coomassie brilliant blue G250 now has better biocompatibility. Four different forms of fluorescence compounds' ultraviolet absorption spectra were identified. It was discovered that FC-2, FC-3, and FC-4, respectively, had double peaks at 483-620 nm. FC-4 had the highest ultraviolet absorption intensity, whereas FC-1 exhibited the most consistent and longest wavelength of ultraviolet absorption. Transmission electron microscopy revealed that the acrylic resin evenly disseminated the Coomassie brilliant blue G250-isorhamnetin complex in an amorphous flocculent form. Human prostate cancer cells (PC3) and human cervical cancer cells (HeLa) were investigated in the (Cell Counting Kit-8) CCK8 experiment under 10 different concentration circumstances, and the proliferation impact was 64.30% and 68.06%, respectively. Shown the complex's strong anti-tumor properties and minimal cytotoxicity. Through in vitro imaging of tumor cells, it was found that FC-1's fluorescent complex has high selectivity and can accurately infiltrate tumor cells, proving that it is biocompatible. The design not only addresses the issue of isorhamnein-Coomassie Bright Blue G250's bioavailability, but it also has an effective visual fluorescence targeting effect.
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Affiliation(s)
- Jiangpeng Hu
- Affiliated Peoples Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Bo Teng
- Affiliated Peoples Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Zhipeng Xu
- Affiliated Peoples Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yuanye Wan
- Affiliated Peoples Hospital, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Guofan Jin
- School of Pharmacy, Jiangsu University, Zhenjiang, China
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Wang X, Wei C, Fan W, Sun L, Zhang Y, Sun Q, Liu Y, Liu J. Advanced Lung Cancer Inflammation Index for Predicting Prognostic Risk for Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. J Inflamm Res 2023; 16:3631-3641. [PMID: 37641701 PMCID: PMC10460579 DOI: 10.2147/jir.s421021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 08/15/2023] [Indexed: 08/31/2023] Open
Abstract
Purpose The decreased advanced lung cancer inflammation index (ALI), defined as body mass index (BMI) * albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR), is an independent prognostic risk factor for overall survival in gastric, lung, and colorectal cancers. This study aimed to investigate the value of ALI in predicting the risk of major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS). Patients and Methods A total of 1624 patients with ACS undergoing percutaneous coronary intervention (PCI) were consecutively enrolled between January 2016 and December 2018. Follow-up data were collected at 1, 3, 6, and 12 months and annually thereafter. The primary endpoints were MACEs. All endpoints were defined as all-cause mortality, recurrent angina pectoris, restenosis/intra stent thrombosis, stroke, heart failure, and all-cause bleeding. Results The MACEs group and non-MACEs group showed significant differences in patients with age >65 years (28 [50.0%] vs 319 [23.7%]), history of heart failure (16 [28.6%] vs 127 [9.4%]), history of ischemic stroke (14 [25.0%] vs 186 [13.8%]), history of cardiogenic shock (6 [10.71%] vs 16 [1.19%]), left ventricular ejection fraction <40% (8 [14.29%] vs 33 [2.46%]), and ALI <343.96 (44 [78.65%] vs 680 [50.60%]) (all p<0.001). The optimal cut-off value for ALI was 334.96. The area under the curve (AUC) of the 1-, 2-, 3-, and 5-year was 0.560, 0.577, 0.665, and 0.749, respectively. The survival rate was significantly lower in the low ALI group than in the high ALI group (log-rank p<0.001). Low ALI was an independent risk factor for the long-term prognosis of patients with ACS after PCI, univariate HR: 3.671, 95% CI: 1.938-6.953, p<0.001; multivariate HR: 3.009, 95% CI: 1.57-5.769, p=0.001. Conclusion ALI score less than 334.96 is an independent prognostic risk factor for patients with ACS undergoing PCI and may be a novel marker for clinical practice.
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Affiliation(s)
- Xinchen Wang
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
| | - Chen Wei
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
| | - Wenjun Fan
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
| | - Lixian Sun
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
| | - Ying Zhang
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
| | - Qiyu Sun
- Department of Clinical Laboratory, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China
| | - Yixiang Liu
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
| | - Jingyi Liu
- Department of Cardiology, The Affiliated Hospital of Chengde Medical University, The Chengde Institute of Cardiovascular Diseases, Chengde, Hebei, 067000, People’s Republic of China
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Manohar-Sindhu S, Merfeld-Clauss S, Goddard Y, March KL, Traktuev DO. Diminished vasculogenesis under inflammatory conditions is mediated by Activin A. Angiogenesis 2023; 26:423-436. [PMID: 36977946 DOI: 10.1007/s10456-023-09873-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: 12/09/2022] [Accepted: 03/06/2023] [Indexed: 03/30/2023]
Abstract
Severe inflammatory stress often leads to vessel rarefaction and fibrosis, resulting in limited tissue recovery. However, signaling pathways mediating these processes are not completely understood. Patients with ischemic and inflammatory conditions have increased systemic Activin A level, which frequently correlates with the severity of pathology. Yet, Activin A's contribution to disease progression, specifically to vascular homeostasis and remodeling, is not well defined. This study investigated vasculogenesis in an inflammatory environment with an emphasis on Activin A's role. Exposure of endothelial cells (EC) and perivascular cells (adipose stromal cells, ASC) to inflammatory stimuli (represented by blood mononuclear cells from healthy donors activated with lipopolysaccharide, aPBMC) dramatically decreased EC tubulogenesis or caused vessel rarefaction compared to control co-cultures, concurrent with increased Activin A secretion. Both EC and ASC upregulated Inhibin Ba mRNA and Activin A secretion in response to aPBMC or their secretome. We identified TNFα (in EC) and IL-1β (in EC and ASC) as the exclusive inflammatory factors, present in aPBMC secretome, responsible for induction of Activin A. Similar to ASC, brain and placental pericytes upregulated Activin A in response to aPBMC and IL-1β, but not TNFα. Both these cytokines individually diminished EC tubulogenesis. Blocking Activin A with neutralizing IgG mitigated detrimental effects of aPBMC or TNFα/IL-1β on tubulogenesis in vitro and vessel formation in vivo. This study delineates the signaling pathway through which inflammatory cells have a detrimental effect on vessel formation and homeostasis, and highlights the central role of Activin A in this process. Transitory interference with Activin A during early phases of inflammatory or ischemic insult, with neutralizing antibodies or scavengers, may benefit vasculature preservation and overall tissue recovery.
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Affiliation(s)
- Sahana Manohar-Sindhu
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, UF College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100277, Gainesville, FL, 32610, USA
| | - Stephanie Merfeld-Clauss
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, UF College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100277, Gainesville, FL, 32610, USA
| | - Yana Goddard
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, UF College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100277, Gainesville, FL, 32610, USA
| | - Keith L March
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, UF College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100277, Gainesville, FL, 32610, USA
| | - Dmitry O Traktuev
- UF Center for Regenerative Medicine, Division of Cardiovascular Medicine, Department of Medicine, UF College of Medicine, University of Florida, 1600 SW Archer Road, PO Box 100277, Gainesville, FL, 32610, USA.
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10
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Classes of Lipid Mediators and Their Effects on Vascular Inflammation in Atherosclerosis. Int J Mol Sci 2023; 24:ijms24021637. [PMID: 36675152 PMCID: PMC9863938 DOI: 10.3390/ijms24021637] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/06/2023] [Accepted: 01/08/2023] [Indexed: 01/18/2023] Open
Abstract
It is commonly believed that the inactivation of inflammation is mainly due to the decay or cessation of inducers. In reality, in connection with the development of atherosclerosis, spontaneous decay of inducers is not observed. It is now known that lipid mediators originating from polyunsaturated fatty acids (PUFAs), which are important constituents of all cell membranes, can act in the inflamed tissue and bring it to resolution. In fact, PUFAs, such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are precursors to both pro-inflammatory and anti-inflammatory compounds. In this review, we describe the lipid mediators of vascular inflammation and resolution, and their biochemical activity. In addition, we highlight data from the literature that often show a worsening of atherosclerotic disease in subjects deficient in lipid mediators of inflammation resolution, and we also report on the anti-proteasic and anti-thrombotic properties of these same lipid mediators. It should be noted that despite promising data observed in both animal and in vitro studies, contradictory clinical results have been observed for omega-3 PUFAs. Many further studies will be required in order to clarify the observed conflicts, although lifestyle habits such as smoking or other biochemical factors may often influence the normal synthesis of lipid mediators of inflammation resolution.
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11
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Henein MY, Vancheri S, Longo G, Vancheri F. The Role of Inflammation in Cardiovascular Disease. Int J Mol Sci 2022; 23:12906. [PMID: 36361701 PMCID: PMC9658900 DOI: 10.3390/ijms232112906] [Citation(s) in RCA: 226] [Impact Index Per Article: 75.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/15/2022] [Accepted: 10/24/2022] [Indexed: 07/21/2023] Open
Abstract
Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1β, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.
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Affiliation(s)
- Michael Y. Henein
- Institute of Public Health and Clinical Medicine, Umea University, 90187 Umea, Sweden
- Institute of Environment & Health and Societies, Brunel University, Middlesex SW17 0RE, UK
- Molecular and Clinical Sciences Research Institute, St. George’s University, London UB8 3PH, UK
| | - Sergio Vancheri
- Interventional Neuroradiology Department, Besançon University Hospital, 25000 Besançon, France
| | - Giovanni Longo
- Cardiovascular and Interventional Department, S.Elia Hospital, 93100 Caltanissetta, Italy
| | - Federico Vancheri
- Department of Internal Medicine, S.Elia Hospital, 93100 Caltanissetta, Italy
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12
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Atherogenesis, Transcytosis, and the Transmural Cholesterol Flux: A Critical Review. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:2253478. [PMID: 35464770 PMCID: PMC9023196 DOI: 10.1155/2022/2253478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/19/2022] [Accepted: 03/23/2022] [Indexed: 11/17/2022]
Abstract
The recently described phenomenon of cholesterol-loaded low-density lipoproteins (LDL) entering the arterial wall from the lumen by transcytosis has been accepted as an alternative for the long-held concept that atherogenesis involves only passive LDL movement across an injured or dysfunctional endothelial barrier. This active transport of LDL can now adequately explain why plaques (atheromas) appear under an intact, uninjured endothelium. However, the LDL transcytosis hypothesis is still questionable, mainly because the process serves no clear physiological purpose. Moreover, central components of the putative LDL transcytosis apparatus are shared by the counter process of cholesterol efflux and reverse cholesterol transport (RCT) and therefore can essentially create an energy-wasting futile cycle and paradoxically be pro- and antiatherogenic simultaneously. Hence, by critically reviewing the literature, we wish to put forward an alternative interpretation that, in our opinion, better fits the experimental evidence. We assert that most of the accumulating cholesterol (mainly as LDL) reaches the intima not from the lumen by transcytosis, but from the artery's inner layers: the adventitia and media. We have named this directional cholesterol transport transmural cholesterol flux (TCF). We suggest that excess cholesterol, diffusing from the avascular (i.e., devoid of blood and lymph vessels) media's smooth muscle cells, is cleared by the endothelium through its apical membrane. A plaque is formed when this cholesterol clearance rate lags behind its rate of arrival by TCF.
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13
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Dasagrandhi D, Muthuswamy A, Swaminathan JK. Atherosclerosis: nexus of vascular dynamics and cellular cross talks. Mol Cell Biochem 2022; 477:571-584. [PMID: 34845570 DOI: 10.1007/s11010-021-04307-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/17/2021] [Indexed: 01/11/2023]
Abstract
Cardiovascular diseases (CVDs) are the foremost cause of mortality worldwide. Atherosclerosis is the underlying pathology behind CVDs. Atherosclerosis is manifested predominantly by lipid deposition, plaque formation, and inflammation in vascular intima. Initiation and progression of plaque require many years. With aging, atherosclerotic plaques become vulnerable. Localization of these plaques in the coronary artery leads to myocardial infarction. A complete understanding of the pathophysiology of this multifaceted disease is necessary to achieve the clinical goal to provide early diagnosis and the best therapeutics. The triggering factors of atherosclerosis are biomechanical forces, hyperlipidemia, and chronic inflammatory response. The current review focuses on crucial determinants involved in the disease, such as location, hemodynamic factors, oxidation of low-density lipoproteins, and the role of endothelial cells, vascular smooth muscle cells, and immune cells, and better therapeutic targets.
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Affiliation(s)
- Divya Dasagrandhi
- Drug Discovery and Molecular Cardiology Laboratory, Department of Bioinformatics, Bharathidasan University, Tiruchirappalli, 620024, India
| | - Anusuyadevi Muthuswamy
- Molecular Neurogerontology Laboratory, Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 620024, India
| | - Jayachandran Kesavan Swaminathan
- Drug Discovery and Molecular Cardiology Laboratory, Department of Bioinformatics, Bharathidasan University, Tiruchirappalli, 620024, India.
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14
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Webberley TS, Masetti G, Baker LM, Dally J, Hughes TR, Marchesi JR, Jack AA, Plummer SF, Ramanathan G, Facey PD, Michael DR. The Impact of Lab4 Probiotic Supplementation in a 90-Day Study in Wistar Rats. Front Nutr 2021; 8:778289. [PMID: 34901123 PMCID: PMC8656110 DOI: 10.3389/fnut.2021.778289] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/02/2021] [Indexed: 12/11/2022] Open
Abstract
The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies in silico, in vitro, and in vivo suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol via the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.
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Affiliation(s)
| | | | - Laura M Baker
- Swansea University Medical School, Swansea University, Swansea, United Kingdom
| | | | - Timothy R Hughes
- Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - Julian R Marchesi
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
| | | | | | - Guru Ramanathan
- Pharmacology based Clinical Trials, Pennington Biomedical Research Centre, Baton Rouge, LA, United States
| | - Paul D Facey
- Swansea University Medical School, Swansea University, Swansea, United Kingdom
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15
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Borovac JA, Leth-Olsen M, Kumric M, D'Amario D, Schwarz K, Glavas D, Bozic J. Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence. Eur J Clin Pharmacol 2021; 78:111-126. [PMID: 34423376 DOI: 10.1007/s00228-021-03196-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/26/2021] [Indexed: 12/27/2022]
Abstract
PURPOSE We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.
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Affiliation(s)
- Josip A Borovac
- Department of Pathophysiology, School of Medicine, University of Split, Split, Croatia. .,Clinic for Heart and Cardiovascular Diseases, University Hospital of Split (KBC Split), Split, Croatia.
| | - Mette Leth-Olsen
- Department of Pathophysiology, School of Medicine, University of Split, Split, Croatia
| | - Marko Kumric
- Department of Pathophysiology, School of Medicine, University of Split, Split, Croatia
| | - Domenico D'Amario
- Department of Cardiovascular and Thoracic Sciences, IRCCS Fondazione Policlinico A. Gemelli, Universita Cattolica Sacro Cuore, Rome, Italy
| | - Konstantin Schwarz
- Department of Internal Medicine 3, Karl Landsteiner University of Health Sciences, University Hospital St, Pölten, Krems, Austria
| | - Duska Glavas
- Clinic for Heart and Cardiovascular Diseases, University Hospital of Split (KBC Split), Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, School of Medicine, University of Split, Split, Croatia
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16
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Wang H, Jiang M, Li X, Zhao Y, Shao J, Liu Z, Lin L, Xu Q, Wang L, Lu X, Zhang H, Chen Y, Zhang R. Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis. Front Cardiovasc Med 2021; 8:726341. [PMID: 34513960 PMCID: PMC8424052 DOI: 10.3389/fcvm.2021.726341] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 07/28/2021] [Indexed: 11/16/2022] Open
Abstract
Background: Anti-inflammatory therapy has been proposed as a promising treatment for coronary heart disease (CHD) that could reduce residual inflammation risk (RIR) and therefore major adverse cardiovascular events. We implemented a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical benefits of anti-inflammatory agents in patients with CHD based on secondary cardiovascular prevention. Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases for RCTs (published between Jan 1, 1950, and June 1, 2021; no language restrictions) that focused on anti-inflammatory therapy for coronary heart disease. Our primary end points of interest were a composite of all-cause death, recurrent myocardial infarction and stroke. We processed pooled data using a random-effects model. Results: Of 1497 selected studies, 18 studies with 67,449 participants met our inclusion criteria and were included in the present meta-analysis. Comparing anti-inflammatory agents with placebo, there was no significant decrease in risk of primary end points, secondary end points, all-cause mortality, cardiac mortality, recurrent myocardial infarction, stroke or revascularization. Further subgroup analysis indicated that anti-inflammatory agents led to a significant reduction in secondary end points (OR 0.87, CI 0.77-0.99; P = 0.03), recurrent myocardial infarction (OR 0.86, CI 0.78-0.95; P = 0.003) and revascularization (OR 0.81, CI 0.70-0.92; P = 0.001) in patients with stable CHD compared with placebo. Moreover, stable CHD patients had a lower propensity for recurrent myocardial infarction than acute coronary syndrome (ACS) patients when using anti-inflammatory agents (P = 0.03). The colchicine subgroup analysis showed that colchicine yielded a promising reduction in the primary end points (OR 0.81, CI 0.70-0.95; P = 0.009) compared with placebo. Anti-inflammatory agents were associated with a higher risk of infection (OR 1.13, CI 1.03-1.23; P = 0.007) and negligible effects on cancers (OR 0.98, CI 0.90-1.06; P = 0.61). Conclusion: Anti-inflammatory agents appear to have beneficial effects in reducing the risk of recurrent myocardial infarction in patients with stable CHD, albeit at the cost of increased infection. Notably, colchicine demonstrates a promising cardioprotective effect with a lower incidence of major cardiovascular events and thus is a potential therapeutic strategy for stable CHD patients. Systematic Review Registration: PROSPERO, identifier CRD42021245514.
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Affiliation(s)
- Haiming Wang
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Min Jiang
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Xin Li
- Department of Health Services, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yunzhang Zhao
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Junjie Shao
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Zifan Liu
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Lejian Lin
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Qiang Xu
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Lin Wang
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Xuechun Lu
- Department of Hematology, The Second Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Haomin Zhang
- Department of Hematology, The Second Medical Center of Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
| | - Yundai Chen
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
- *Correspondence: Yundai Chen
| | - Ran Zhang
- Department of Cardiovascular Medicine, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China
- Ran Zhang
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