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.

Interleukin‐37 and Dendritic Cells Treated With Interleukin‐37 Plus Troponin I Ameliorate Cardiac Remodeling After Myocardial Infarction

“…It has been reported that toll‐like receptor 4 mediates maladaptive left ventricular (LV) remodeling and impairs cardiac function after MI . Moreover, experimental studies from our laboratory demonstrated that interleukin (IL)–17A promotes ventricular remodeling after MI . These findings suggest that excessive immune‐mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling.…”

“…4 Moreover, experimental studies from our laboratory demonstrated that interleukin (IL)-17A promotes ventricular remodeling after MI. 5 These findings suggest that excessive immune-mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling. Paradoxically, immunosuppressive therapy with methylprednisolone resulted in increased catastrophic mortality due to cardiac rupture.…”

IL-17A blockade or deficiency does not affect progressive renal fibrosis following renal ischaemia reperfusion injury in mice

“…Studies of the pro‐fibrotic effects of IL‐17 in the lung heart and liver have been undertaken. In the latter, IL‐17‐mediated liver fibrosis through hepatic stellate cell activation .…”

“…Despite the protection of IL-17A -/mice in a mild IRI model, we could not see any effect on renal fibrosis over a period of 3 weeks in our study. Studies of the pro-fibrotic effects of IL-17 in the lung [28] heart [29] and liver [30] have been undertaken. In the latter, IL-17-mediated liver fibrosis through hepatic stellate cell activation.…”

Role of Inflammation in Heart Failure

“…However, the role of IL-17 in HF progression is unclear. Additionally, IL-17A has been shown to induce cardiac myocyte apoptosis in experimental HF [20], though anti-IL-17 therapies have not yet been studied in humans.…”