The Role of Exogenous Agomir-133 in the Improvement of Cardiac Pathological Remodeling Induced by Treadmill Exercise

Objective: To observe the regulatory effect of exercise on the expression of endogenous miR-133 in cardiac pathological remodeling rats induced by abdominal aortic coarctation(AAC); and then to investigate the effects of exercise on cardiac pathological remodeling and myocardial apoptosis through exogenous agomir-133 and explore the possible mechanisms. Methods: SD rats were randomly divided into four groups: sham operation group(CON), abdominal aortic coarctation group(AAC), abdominal aortic coarctation+treadmill exercise+agomir-NC group(A+E+NC) and abdominal aortic coarctation+treadmill exercise+agomir-133 group(A+E+agomir-133), there were 5 rats in each group. The CON group only opened the abdominal cavity to separate the intestinal canal, but did not ligate. Four weeks after operation, A+E+NC and A+E+agomir-133 groups were beginning to run on the treadmill for four weeks with the exogenous injection of agomir-NC and agomir-133, respectively. Cardiac function was detected by echocardiography at the next day after the last training; blood samples, heart and gastrocnemius muscle samples were collected for the following detections. The H&E staining was used to observe the morphological changes of myocardium and gastrocnemius muscle fibers; myocardial fibrosis was observed by Sirius red staining; myocardial apoptosis was observed by TUNEL; ELISA method was used to detect the concentration of myostatin(MSTN) in plasma; Real-time PCR was used to measure the expression of miR-133, atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), MSTN, collagen I and III, Bcl2-associated X(Bax) and Bcell lymphoma-2(Bcl-2) in serum and myocardium. Results: In AAC group, the cardiac pathological remodeling was occurred, the cardiac function was decreased, the cross-sectional area of cardiomyocytes, fibrosis and apoptosis were increased, the expression of myocardial miR-133 was decreased in myocardium but increased in plasma. After 4 weeks of treadmill exercise, cardiac pathological remodeling was improved, cardiac function was recovered, the cross-sectional area of cardiomyocytes was decreased, fibrosis and apoptosis was decreased, the expression of miR-133 was increased in myocardium and decreased in plasma. After administration of agomir-133, the effect of exercise on cardiac pathological remodeling was disappeared, cardiac function was decreased, myocardial fibrosis and apoptosis was increased, and the muscle atrophy was occurred in rats. Conclusions: Treadmill exercise can significantly improve myocardial hypertrophy and fibrosis, inhibit cardiomyocyte apoptosis, increase the expression of myocardial miR-133 and reduce the level of miR-133 in circulation. Exogenous administration of agomir-133 counteracted the improvement of cardiac pathological remodeling and anti apoptotic effect of exercise, which may be related to peripheral mechanisms.