Moderate exercise relieves heart failure-induced skeletal muscle atrophy through the inhibition of MAPK/SOCS3 signaling.

Heart failure (HF) is a structural or functional abnormality of the heart, often accompanied by skeletal muscle atrophy and other complications. Exercise plays an important role in preventing muscle atrophy. However, the underlying molecular mechanisms related to skeletal muscle atrophy in HF still remain poorly understood. In this study, we constructed an HF rat model by abdominal aortic coarctation (AAC) and a C2C12 muscle atrophy cell model induced by angiotensin II (Ang II). The relevant protein expressions were analyzed using western blotting. The damage of myocardial tissue, gastrocnemius tissue and cells were assessed through echocardiography, ELISA, HE staining, and immunofluorescence staining. Findings from this study indicated that moderate exercise has beneficial effects on pathological damage in the myocardial and gastrocnemius tissues of rats, resulting in a reduction of NT-proBNP levels in the blood. Furthermore, it was observed that the expression levels of MAFbx and MuRF1 were downregulated, while MHC and MyoD expressions were elevated, and the expression of endoplasmic reticulum stress (ERS)-related proteins GRP78, p-eIF2α, p-IRE1α, p-PERK, CHOP, ATF6 was inhibited, and finally alleviated HF-induced skeletal muscle atrophy. The mechanism involves moderate exercise working to alleviate ERS by inhibiting the MAPK/SOCS3 signaling pathway, thus alleviating skeletal muscle atrophy induced by HF. Our study elucidates the positive role of moderate exercise in HF-induced skeletal muscle atrophy, reveals its potential molecular mechanism, and provides a new scientific basis for the comprehensive treatment of skeletal muscle atrophy in HF.