The anti-aging protein Klotho has been associated with cardiovascular health protection. Nevertheless, the protective mechanism remains unknown. The present study is aimed at exploring the effect of Klotho on cardiac remodeling and its potential mechanism in mice with myocardial infarction (MI). We used left anterior coronary artery descending ligation to develop an MI model for in vivo analyses. In contrast, H9C2 cells and cardiac fibroblasts were used to establish the oxygen–glucose deprivation (OGD) model in in vitro analyses. In vivo and in vitro models were treated with Klotho. Compound C, an AMPK signaling inhibitor, was used to determine whether Klotho’s effects are mediated through the AMPK/mTOR signaling pathway. Echocardiography, Masson trichrome staining, immunofluorescence, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot were used to detect the related indicators. The findings of the in vivo model indicate that Klotho treatment improved the mice’s cardiac function, reduced cardiac fibrosis, and attenuated myocardial inflammatory factors, ferroptosis, and oxidative stress. The results of the in vitro model were in line with the findings of in vivo modeling. An AMPK inhibitor, Compound C, reversed all these effects. In conclusion, Klotho potentially improves cardiac remodeling in MI mice by regulating AMPK/mTOR signaling, demonstrating Klotho as an effective MI therapeutic agent.

抗衰老蛋白 Klotho 与心血管健康保护有关。然而，保护机制仍然未知。本研究旨在探讨Klotho对心肌梗死（MI）小鼠心脏重构的影响及其潜在机制。我们使用左冠状动脉前降支结扎来开发用于体内分析的 MI 模型。相比之下，H9C2细胞和心脏成纤维细胞用于在体外分析中建立氧糖剥夺（OGD）模型。用 Klotho 处理体内和体外模型。化合物 C 是一种 AMPK 信号传导抑制剂，用于确定 Klotho 的作用是否是通过 AMPK/mTOR 信号传导途径介导的。超声心动图、马森三色染色、免疫荧光、免疫组织化学、采用实时聚合酶链式反应（RT-PCR）、蛋白质印迹法检测相关指标。体内模型的结果表明，Klotho 治疗改善了小鼠的心脏功能，减少了心脏纤维化，并减轻了心肌炎症因子、铁死亡和氧化应激。体外模型的结果与体内模型的结果一致。AMPK 抑制剂化合物 C 可以逆转所有这些影响。总之，Klotho 通过调节 AMPK/mTOR 信号传导可能改善 MI 小鼠的心脏重塑，证明 Klotho 是一种有效的 MI 治疗剂。并减弱心肌炎症因子、铁死亡和氧化应激。体外模型的结果与体内模型的结果一致。AMPK 抑制剂化合物 C 可以逆转所有这些影响。总之，Klotho 通过调节 AMPK/mTOR 信号传导可能改善 MI 小鼠的心脏重塑，证明 Klotho 是一种有效的 MI 治疗剂。并减弱心肌炎症因子、铁死亡和氧化应激。体外模型的结果与体内模型的结果一致。AMPK 抑制剂化合物 C 可以逆转所有这些影响。总之，Klotho 通过调节 AMPK/mTOR 信号传导可能改善 MI 小鼠的心脏重塑，证明 Klotho 是一种有效的 MI 治疗剂。