Cardioprotection of Klotho against myocardial infarction-induced heart failure through inducing autophagy

Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. The aim of this study was to investigate the role of Klotho in cardiac function and remodeling as well as its underlying mechanism in mice with MI-induced HF. For in vivo analyses, MI or sham MI were established in C57BL/6 mice. For in vitro analyses, the H9C2 cells were used to establish a model of oxygen glucose deprivation (OGD). The In vivo and in vitro models were treated with or without Klotho. 3-methyladenine (3-MA) was used to inhibit autophagy in MI mice and H9C2 cells. Cardiac function, cardiac fibrosis, cardiomyocyte autophagy, inflammatory cytokines and myocardial apoptosis were measured. Our results revealed that Klotho significantly improved cardiac function and remodeling, reduced cardiac fibrosis, and suppressed the levels of myocardial inflammatory factors and apoptosis in MI-induced HF model. Klotho enhanced autophagy in cardiomyocytes and inhibited PI3K/AKT/mTOR signaling pathway in the mouse model of MI. Similar observations were made in the OGD model after treatment with Klotho. However, the cardioprotective effects of Klotho was significantly suppressed by 3-MA. Our data indicate that Klotho exerts its cardioprotective effects against MI-induced HF by inducing autophagy through the inhibition of PI3k/AKT/mTOR signaling pathway. •Heart failure after myocardial infarction could lead to cardiac fibrosis, cardiac dysfunction and cell apoptosis.•Klotho could improve myocardial hypertrophy, cardiac function, cardiac fibrosis and inhibit cell apoptosis.•Klotho could activate autophagy and inhibit PI3K/AKT/mTOR signaling.•3-methyladenine (3-MA) could suppress the effects of Klotho.