IL-17A promotes ventricular remodeling after myocardial infarction
IL-17A promotes ventricular remodeling after myocardial infarction
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DOI：
10.1007/s00109-014-1176-8
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发表时间：
2014-10-01
影响因子：
4.7
通讯作者：
Cheng, Xiang
中科院分区：
文献类型：
--
作者：
Zhou, Su-Feng;Yuan, Jing;Cheng, Xiang
炎症反应在心肌梗死（MI）后不良心室重构的发病机制中起重要作用。我们之前已经证明白细胞介素(IL)-17A在心肌缺血/再灌注损伤和病毒性心肌炎中起致病作用。然而，IL-17A在心肌梗死后重构中的作用及其相关机制尚未完全阐明。永久性结扎C57BL/6小鼠左冠状动脉前降支诱导急性心肌梗死。IL-17A的表达显著加重了早期和晚期心室重构，表现为梗死面积增加、心功能恶化、心肌纤维化增加和心肌细胞凋亡。相比之下，遗传IL-17A缺乏具有相反的效果。进一步的体外研究表明，IL-17A通过激活p38、p53磷酸化和Bax再分布诱导新生儿心肌细胞（来自C57BL/6小鼠）凋亡。这些数据表明，IL-17A通过p38丝裂原活化蛋白激酶(MAPK)-p53- bax信号通路诱导心肌细胞凋亡，促进心肌梗死后早期和晚期心室重构。IL-17A可能是预防心肌梗死后心力衰竭的重要靶点。我们证明IL-17A在心肌梗死后重构的早期和晚期都起着致病作用。IL-17A诱导小鼠心肌细胞凋亡。IL-17A通过p38 MAPK-p53-Bax信号通路诱导小鼠心肌细胞凋亡。
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.aEuro cent We demonstrated that IL-17A plays a pathogenic role both in the early and late stages of post-MI remodeling.aEuro cent IL-17A induces murine cardiomyocyte apoptosis.aEuro cent IL-17A induces murine cardiomyocyte apoptosis through the p38 MAPK-p53-Bax signaling pathway.