title: IL-17A promotes ventricular remodeling after myocardial infarction.
abstract: Inflammatory responses play an important role in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We previously demonstrated that interleukin (IL)-17A plays a pathogenic role in myocardial ischemia/reperfusion injury and viral myocarditis. However, the role of IL-17A in post-MI remodeling and the related mechanisms have not been fully elucidated. Acute MI was induced by permanent ligation of the left anterior descending coronary artery in C57BL/6 mice. Repletion of IL-17A significantly aggravated both early- and late-phase ventricular remodeling, as demonstrated by increased infarct size, deteriorated cardiac function, increased myocardial fibrosis, and cardiomyocyte apoptosis. By contrast, genetic IL-17A deficiency had the opposite effect. Additional studies in vitro indicated that IL-17A induces neonatal cardiomyocyte (from C57BL/6 mice) apoptosis through the activation of p38, p53 phosphorylation, and Bax redistribution. These data demonstrate that IL-17A induces cardiomyocyte apoptosis through the p38 mitogen-activated protein kinase (MAPK)-p53-Bax signaling pathway and promotes both early- and late-phase post-MI ventricular remodeling. IL-17A might be an important target in preventing heart failure after MI. Key message: We demonstrated that IL-17A plays a pathogenic role both in the early and late stages of post-MI remodeling. IL-17A induces murine cardiomyocyte apoptosis. IL-17A induces murine cardiomyocyte apoptosis through the p38 MAPK-p53-Bax signaling pathway.
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China.
authors: Su-Feng
authors: SF
authors: Zhou
authors: Jing
authors: J
authors: Yuan
authors: Meng-Yang
authors: MY
authors: Liao
authors: Ni
authors: N
authors: Xia
authors: Ting-Ting
authors: TT
authors: Tang
authors: Jing-Jing
authors: JJ
authors: Li
authors: Jiao
authors: J
authors: Jiao
authors: Wen-Yong
authors: WY
authors: Dong
authors: Shao-Fang
authors: SF
authors: Nie
authors: Zheng-Feng
authors: ZF
authors: Zhu
authors: Wen-Cai
authors: WC
authors: Zhang
authors: Bing-Jie
authors: BJ
authors: Lv
authors: Hong
authors: H
authors: Xiao
authors: Qing
authors: Q
authors: Wang
authors: Xin
authors: X
authors: Tu
authors: Yu-Hua
authors: YH
authors: Liao
authors: Guo-Ping
authors: GP
authors: Shi
authors: Xiang
authors: X
authors: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005355:Fibrosis; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D020381:Interleukin-17; D012333:RNA, Messenger; D053722:Receptors, Interleukin-17; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases