Exercise Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating Endoplasmic Reticulum Stress and Mitophagy Through M Acetylcholine Receptor.

Adaptive changes in the heart by exercise have been shown to reduce the risk of cardiovascular disease, and M Acetylcholine receptor (MAChR), a receptor abundantly present on cardiac parasympathetic nerves, is closely associated with the development of cardiovascular disease. The present study intends to investigate whether exercise can regulate endoplasmic reticulum stress (ERS) and mitophagy through MAChR to resist myocardial ischemia-reperfusion (I/R) injury and to elucidate its mechanism of action. Exercise enhanced parasympathetic nerve function and increased myocardial MAChR protein expression in I/R rats. In addition, it promoted the protein expression of MFN2 and inhibited the expression of Drp1, Chop, PINK1/Parkin, and PERK/eIF2α/ATF4 signaling pathways, effectively reducing mitophagy, ERS, and apoptosis. At the cellular level, 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced hypoxia/reoxygenation (H/R)-induced ERS through the downregulated expression of PERK/eIF2α/ATF4 pathway proteins in H9C2 cardiomyocytes. When intervened with MAChR inhibitors, the levels of ERS and phosphorylation levels of the PERK/eIF2α/ATF4 pathway were increased in H/R cells. Exercise intervention activated the parasympathetic state in rats. It inhibited myocardial mitophagy and ERS levels, and reduced myocardial apoptosis through MAChR, thereby resisting I/R-induced myocardial injury and improving cardiac function. 40, 209-221.