J Mol Med (2014) 92:1105–1116 DOI 10.1007/s00109-014-1176-8

ORIGINAL ARTICLE

IL-17A promotes ventricular remodeling after myocardial infarction Su-Feng Zhou & Jing Yuan & Meng-Yang Liao & Ni Xia & Ting-Ting Tang & Jing-Jing Li & Jiao Jiao & Wen-Yong Dong & Shao-Fang Nie & Zheng-Feng Zhu & Wen-Cai Zhang & Bing-Jie Lv & Hong Xiao & Qing Wang & Xin Tu & Yu-Hua Liao & Guo-Ping Shi & Xiang Cheng

Received: 28 December 2013 / Revised: 2 May 2014 / Accepted: 23 May 2014 / Published online: 27 June 2014 # Springer-Verlag Berlin Heidelberg 2014

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 IL17A 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 mitogenactivated 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.

Keywords IL-17A . Myocardial infarction . Ventricular remodeling . Heart failure . Apoptosis

Su-Feng Zhou, Jing Yuan, and Meng-Yang Liao contributed equally to this study. Electronic supplementary material The online version of this article (doi:10.1007/s00109-014-1176-8) contains supplementary material, which is available to authorized users. S.

IL-17A promotes ventricular remodeling after myocardial infarction.

Inflammatory responses play an important role in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We previously de...
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