Aerobic exercise ameliorates cardiac hypertrophy by regulating mitochondrial quality control and endoplasmic reticulum stress through M₂AChR

Abstract

Aerobic exercise increases M 2 AChR, which thus improves cardiac function in cardiovascular disease (CVD) rats. This study aimed to determine whether aerobic exercise could ameliorate pressure overload-induced heart hypertrophy through M 2 AChR, and to elucidate the underlying mechanisms of action. Mice were used to establish the myocardial hypertrophy model by transverse aortic constriction (TAC), and subjected to 2, 4, and 8 weeks of moderate-intensity aerobic exercise and choline intervention (14 mg/kg/day). Our results showed that 4 and 8 weeks of exercise and choline intervention reduced excessive mitochondrial fission and autophagy of myocardial mitochondria, thereby improving the ultrastructure and function of mitochondria after TAC. Moreover, 8-week exercise and choline intervention have enhanced parasympathetic function and promoted the expression of M 2 AChR. In addition, 8-week exercise and choline intervention also inhibited the protein expression of myocardial MFN2, PERK/eIF2α/ATF4, and NLRP3/caspase-1/IL-1β signaling pathways, thereby effectively reducing mitochondrial fusion, endoplasmic reticulum stress, and inflammation. Taken together, these data suggest that pressure overload led to cardiac hypertrophy, cardiac dysfunction, and decreased parasympathetic function in cardiac tissues. Aerobic exercise attenuated cardiac dysfunction by modulating the expression of proteins involved in mitochondrial quality control, and induced endoplasmic reticulum stress and inflammation, thereby reducing cardiac hypertrophy and improving cardiac function in impaired heart tissues following TAC, which was likely mediated by M 2 AChR activation.

Exercise training improves cardiac function and regulates myocardial mitophagy differently in ischaemic and pressure‐overload heart failure mice

“…In addition, HIF1α in the myocardium of mice with both aetiologies of HF was also significantly reduced in the present study, which was consistent with the decreased HIF1α in the (Chang & Ma, 2017). Our findings confirmed that both MICT and HIIT improved autophagic flux and mitophagy levels in mice with ischaemic and pressure-overload HF, which was partially consistent with previous lesser evidence (Chang & Ma, 2017;Li et al, 2021;Ma et al, 2021;Moradi et al, 2019;Zhao et al, 2018).…”

Mitochondria in Pathological Cardiac Hypertrophy Research and Therapy

“…Interestingly, researchers have recently illustrated the relationship between aerobic exercise and hypertrophy, and they illustrated that in the mice persisting in aerobic exercise, cardiac hypertrophy and dysfunction were greatly improved. Mechanistically, mitochondria from the aerobic exercise group exhibited decreased excessive mitochondrial fission and mitochondrial autophagy, thus restoring mitochondrial ultrastructure and function in response to hypertrophic insults ( 81 ).…”

Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases

“…Overactivation of endoplasmic reticulum stress (ERS) and perturbation of mitochondrial function play a significant role in compensatory cardiac hypertrophy and progression to overt systolic heart failure ( Chaanine et al, 2013 ; Ma et al, 2021 ). Intraperitoneal injection of tunicamycin (TN) is an interesting model that can be used to study the functional effects of cardiac ER stress.…”