Palmitic acid induces cardiomyocyte apoptosis by enhancing the KLF4/cMLCK signaling pathway.

Abstract

Hyperlipidemia and myocardial apoptosis caused by myocardial ischemia are the main causes of high mortality rates in cardiovascular diseases. Previous studies have indicated that Krüppel-like factor 4 (KLF4) is involved in the induction of cardiac myocyte apoptosis under various stress conditions. In current study, we discovered that KLF4 also participates in palmitic acid (PA)-induced cardiac myocyte apoptosis. However, the specific mechanisms by which KLF4 regulates cardiac myocyte apoptosis remain unclear. Cardiac myosin light-chain kinase (cMLCK) is a crucial enzyme involved in regulating cardiac myocyte contraction and is closely associated with the regulation of apoptosis. Here, we employed the lipotoxicity in vitro and in vivo models to explore the potential synergistic role of KLF4 and cMLCK in cardiac myocyte apoptosis. Our findings demonstrate that under the influence of PA, upregulation of KLF4 expression accompanied by downregulation of cMLCK expression leads to cardiomyocyte apoptosis and cell proliferation inhibition. Selective knockdown and overexpression of KLF4 in cardiomyocytes further confirmed the involvement of KLF4 in PA-induced cardiomyocyte apoptosis. Likewise, overexpression of cMLCK alleviated PA-induced cardiac myocyte apoptosis. Our study reveals the pro-apoptotic effect of KLF4 and elucidates the specific mechanism by which the KLF4/cMLCK signaling pathway is involved in PA-induced cardiac myocyte apoptosis, providing new therapeutic targets for cardiovascular disease treatment.