IL-17A Promotes Ventricular Remodeling After Myocardial Infarction And Its Mechanistic Study

Part I:IL-17A promote adverse ventricular remodeling after myocardial infractionAims:Inflammatory responses play an important role in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). This study aims to explore the role of interleukin (IL)-17A in post-MI remodeling and its related mechanism.Methods:In the in vivo experiments, we established the MI model in mice by permanent ligation of the left anterior descending coronary artery. Then, the effects of IL-17A on ventricular remodeling assessed by infarct size, cardiac function, myocardial fibrosis and apoptosis were evaluated after repletion or genetic deficiency of IL-17A. In the in vitro experiments, we focused on the role of IL-17A in cardiomyocyte apoptosis and its detailed mechanisms including caspases activity and their upstream regulators MAPKs, p53and bax.Results: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. In neonatal cardiomyocyte, IL-17A induced p38phosphorylation, which leaded to a p53-dependent bax redistribution, followed by the enhanced mitochondrial permeability, the release of cytochrome C and the activation of caspases3/9, resulting in cell apoptosis.Conclusions:IL-17A promotes both early-and late-phase post-MI ventricular remodeling and induces cardiomyocyte apoptosis through the p38MAPK-p53-Bax signaling pathway. Part II:IL-17A induce cardomyocyte apoptosis through p38MAPK-p53-Bax signaling pathwayAims:This study aims to explore the mechanism of interleukin (IL)-17A inducing cardiomyocytes apoptosis.Methods:In the in vitro experiments, we focused on the role of IL-17A in cardiomyocyte apoptosis and its detailed mechanisms including caspases activity and their upstream regulators MAPKs, p53and bax.Results:In neonatal cardiomyocyte, IL-17A induced p38phosphorylation, which leaded to a p53-dependent bax redistribution, followed by the enhanced mitochondrial permeability, the release of cytochrome C and the activation of caspases3/9, resulting in cell apoptosis.Conclusions:IL-17A induces cardiomyocyte apoptosis through the p38MAPK-p53-Bax signaling pathway.