Aerobic exercise increases M₂AChR, 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 M₂AChR, 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 M₂AChR. 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 M₂AChR activation.

The treatment and prevention of hypertension has been a worldwide medical challenge. The key pathological hallmark of hypertension is altered arterial vascular structure and function, i.e., increased peripheral vascular resistance due to vascular remodeling. The aim of this review is to elucidate the molecular mechanisms of vascular remodeling in hypertension and the protective mechanisms of aerobic exercise against vascular remodeling during the pathological process of hypertension. The main focus is on the mechanisms of oxidative stress and inflammation in the pathological condition of hypertension and vascular phenotypic transformation induced by the trilaminar structure of vascular endothelial cells, smooth muscle cells and extracellular matrix, and the peripheral adipose layer of the vasculature. To further explore the possible mechanisms by which aerobic exercise ameliorates vascular remodeling in the pathological process of hypertension through anti-proliferative, anti-inflammatory, antioxidant and thus inhibiting vascular phenotypic transformation. It provides a new perspective to reveal the intervention targets of vascular remodeling for the prevention and treatment of hypertension and its complications.

Purpose/aim of the study: To investigate the effect and molecular mechanism of endurance and resistance training on synaptic plasticity in chronic stressed depression rats. Materials and methods: Chronic unpredictable mild stress (CUMS) was used to establish depressive rats model. Healthy male SD rats were randomly divided into 4 groups (control, CUMS, AE, and RT). The animals in AE and RT groups were respectively subjected to continuous treadmill running and intermittent weight-bearing treadmill training for 8 weeks after CUMS. Forced swimming test (FST) was used to evaluate behavior of rats. The flow cytometry was used to detect the hippocampal neuronal apoptosis. LTP in hippocampal CA1 region were analyzed by electrophysiology. The expressions of various mRNA and proteins related to synaptic function were measured using RT-PCR, Western blot or immunohistochemistry in the hippocampus. Results: Results shown that rats exhibited depressive behavior after CUMS stimulation, specifically immobility time was increased and swimming time and climbing time were reduced in rats during FST. After training, AE and RT all attenuated CUMS-induced depressive behavior of rats. AE and RT reduced apoptosis rate of hippocampal neuron and increased PS amplitude and fEPSPs slope after CUMS stimulation. After CUMS stimulation, AE promoted mRNA expressions, including BDNF, mTOR, TrkB, Syn, Syp, CaMKIIβ, and DRD5, and increased protein expressions, including IGF-1, PGC-1α, ERRβ, and FNDC5. While RT promoted mRNA expressions, including IGF-1, mTOR, Akt, Syn, and Syp, and improved protein expressions, including IGF-1, IGF-1R, and p-Akt. Conclusions: In conclusion, AE and RT for 8 weeks improved CUMS-induced depressive behavior, neuron injury and synaptic plasticity through regulating different signaling pathways.

Aims: Adaptive changes in the heart by exercise have been shown to reduce the risk of cardiovascular disease, and M2 Acetylcholine receptor(M2AChR), 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 and mitophagy through M2AChR to resist myocardial ischemia-reperfusion(I/R) injury and to elucidate its mechanism of action. Results: Exercise enhanced parasympathetic nerve function and increased myocardial M2AChR 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, endoplasmic reticulum stress, and apoptosis. At the cellular level, AICAR reduced hypoxia/reoxygenation(H/R)-induced endoplasmic reticulum stress through the downregulated expression of PERK/eIF2α/ATF4 pathway proteins in H9C2 cardiomyocytes. When intervened with M2AChR inhibitors, the levels of endoplasmic reticulum stress(ERs) and phosphorylation levels of the PERK/eIF2α/ATF4 pathway were increased in H/R cells. Innovation and Conclusion: Exercise intervention activated the parasympathetic state in rats. It inhibited myocardial mitophagy and endoplasmic reticulum stress levels, and reduced myocardial apoptosis through M2AChR, thereby resisting I/R-induced myocardial injury and improving cardiac function.

To explore the molecular mechanism of aerobic exercise to improve heart failure and to provide a theoretical basis and experimental reference for the treatment of heart failure. Nine-week-old male mice were used to establish a left ventricular pressure overload-induced heart failure model by transverse aortic constriction (TAC). The mice were randomly divided into four groups: a sham group (SHAM), heart failure group (HF), heart failure + SKQ1 group (HS) and heart failure + aerobic exercise group (HE). The mice in the HE group were subjected to moderate-intensity aerobic exercise interventions. The mitochondrion-targeting antioxidant (SKQ1) contains the lipophilic cation TPP, which targets scavenging mitochondrial ROS. The HS group was subjected to SKQ1 (100 nmol/kg/d) interventions, which were initiated 1 week after the surgery, and the interventions lasted 8 weeks. Cardiac function was assessed by ultrasound, cardiomyocyte size by H&E and WGA staining, myocardial fibrosis by Masson’s staining, and myocardial tissue oxidative stress and apoptosis by DHE and TUNEL fluorescence staining, respectively. Western blotting was used to detect the expression of mitochondrial quality control, inflammation, and apoptosis-related proteins. In the cellular level, an in vitro cellular model was established by isolating primary cardiomyocytes from neonatal mice (2–3 days) and intervening with Ang II (1 μM) to mimic heart failure. Oxidative stress and mitochondrial membrane potential were determined in the cardiomyocytes of each group by DHE and JC-1 staining, respectively. Myocardial fibrosis was increased significantly and cardiac function was reduced significantly in the heart failure mice. Aerobic exercise and SKQ1 intervention improved cardiac function and reduced myocardial hypertrophy and myocardial fibrosis in the heart failure mice significantly. Meanwhile, aerobic exercise and SKQ1 intervention reduced the number of DHE-positive particles (p < 0.01) and inhibited myocardial oxidative stress in the heart failure mice significantly. Aerobic exercise also reduced DRP1, Parkin, and BNIP3 protein expression (p < 0.05, p < 0.01), and increased OPA1 and PINK1 protein expression (p < 0.05, p < 0.01) significantly. Moreover, aerobic exercise and SKQ1 intervention decreased the number of TUNEL-positive particles and the expression of inflammation- and apoptosis-related proteins NLRP3, TXNIP, Caspase-1, IL-1β, BAX, BAK, and p53 significantly (p < 0.05, p < 0.01). In addition, the AMPK agonist AICAR and the mitochondria-targeted ROS scavenger (SKQ1) ameliorated AngII-induced mitochondrial fragmentation and decreased mitochondrial membrane potential in cardiomyocytes significantly. It was shown that inhibition of mitochondrial ROS by aerobic exercise, which in turn inhibits mitochondrial damage, improves mitochondrial quality control, and reduces myocardial inflammatory and apoptosis, may be an important molecular mechanism by which aerobic exercise exerts endogenous antioxidant protective effects to improve cardiac function.

The morbidity and mortality of cardiovascular diseases are exceedingly high worldwide. Pathological heart remodeling, which is developed as a result of mitochondrial dysfunction, could ultimately drive heart failure. More recent research target exercise modulation of mitochondrial dysfunction to improve heart failure. Therefore, finding practical treatment goals and exercise programs to improve cardiovascular disease is instrumental. Better treatment options are available with the recent development of exercise and drug therapy. This paper summarizes pathological states of abnormal mitochondrial function and intervention strategies for exercise therapy.