Aerobic Exercise Rehabilitation Training Alleviates Skeletal Muscle Atrophy Caused by Heart Failure in Mice Through the SIRT1/PGC-1α Pathway

To investigate the potential effects of aerobic exercise rehabilitation training (AET) on the progression of myocardial infarction (MI) in a left anterior descending (LAD) coronary artery ligation model in mice, and to explore the underlying mechanisms. MI was induced in male C57BL/6 mice by ligating the LAD coronary artery. After 1 week rest, the mice underwent either adaptive ladder training or treadmill training for 5 consecutive days. The H9C2 cell model was used to simulate AngII-induced myocardial injury, cardiac function was assessed by echocardiography, and gastrocnemius muscle laminin expression was analyzed by immunofluorescence. Skeletal muscle-related gene expression was evaluated by immunoblotting, and the effects of AET on mitochondrial function were assessed using immunoblotting and commercial kits. In addition, JC-1 staining was used to examine mitochondrial dysfunction and further confirm the underlying mechanisms. AET significantly improves cardiac function in MI mice and could mitigate skeletal muscle atrophy in these mice. Further analysis revealed that activation of the SIRT1/PGC-1α pathway by AET enhances mitochondrial function in MI mice. In addition, SIRT1 activation was shown to alleviate skeletal muscle mitochondrial dysfunction induced by heart failure in vitro. AET can alleviate skeletal muscle atrophy induced by heart failure in mice through the SIRT1/PGC-1α pathway.