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.

心肌梗塞 (MI) 是全球心力衰竭 (HF) 最常见的原因。本研究的目的是研究 Klotho 在心肌梗死诱导的 HF 小鼠心脏功能和重塑中的作用及其潜在机制。对于体内分析，在 C57BL/6 小鼠中建立了 MI 或假 MI。对于体外分析，H9C2 细胞用于建立氧葡萄糖剥夺 (OGD) 模型。体内_体外模型使用或不使用 Klotho 进行治疗。3-甲基腺嘌呤 (3-MA) 用于抑制 MI 小鼠和 H9C2 细胞的自噬。测量心脏功能、心脏纤维化、心肌细胞自噬、炎性细胞因子和心肌细胞凋亡。我们的研究结果表明，Klotho 在 MI 诱导的 HF 模型中显着改善了心脏功能和重塑，减少了心脏纤维化，并抑制了心肌炎症因子和细胞凋亡的水平。在 MI 小鼠模型中，Klotho 增强了心肌细胞的自噬并抑制了 PI3K/AKT/mTOR 信号通路。在用 Klotho 治疗后，在 OGD 模型中进行了类似的观察。然而，Klotho 的心脏保护作用被 3-MA 显着抑制。