Aerobic Exercise Suppresses Apoptosis by Promoting Endothelial Exosomes from Cardiomyocytes

Objective: To investigate the effects of exercise intervention on exosomes and inhibition of apoptosis in H9C2 cells.Methods: Left anterior descending ligature(LAD) was used to prepare MI model in C57/BL6 mice, and they were randomly divided into sham operation group(S), myocardial infarction group(MI), myocardial infarction and aerobic exercise group(ME), 8 mice in each group. One week after the surgery, the ME group performed aerobic exercise training for 6 weeks. After training, the echocardiography was used to detect LVIDs, LVIDd, FS, and EF; the myocardial fibrosis was detected by masson staining.HUVEC cells were cultured in an exosome-free medium, and exosomes were extracted to incubate H9C2 cells. AMPK agonist(AICAR, 2 mmol/L, 24 h) and lipopolysaccharide(LPS, 10 μg/m L, 4 h) were used to interfere H9C2 cells. NTA and Western Blotting were used to identify the extracted exosomes; Hoechst 33342 staining and TUNEL were used to detect apoptosis; Western Blotting was used to detect apoptosis-related proteins of Bax, Bcl-2, and cleaved-Caspase3. Results: Compared with MI group, the EF and FS were significantly increased(P<0.05) and expression of apoptotic protein Bax/Bcl-2 and cleaved Caspase3/GAPDH were significantly decreased(P<0.05) in ME group. NTA particle size and Western Blotting were positive for exosomes; no exocytosis was observed in normal cells. Compared with the H9C2 apoptosis group induced by LPS alone, AICAR intervention can significantly promote H9C2 exosome swallowing function. Hoechst 33342 staining and TUNEL detection significantly reduce the number of positive apoptosis, and the expressions of apoptosis-related protein Bax/Bcl-2 and cleaved-Caspase3/GAPDH were decreased significantly. Conclusion: Aerobic exercise significantly inhibited myocardial cell apoptosis and improved cardiac function in myocardial infarction. HUVEC endothelial cells secreted exosomes, and AMPK agonist AICAR significantly promoted in vivo uptake of HUVEC-derived exosomes by H9C2 cardiomyocytes, and inhibited apoptosis of H9C2 cardiomyocytes. It is speculated that exercise training may improve myocardial function by promoting cardiomyocyte exosomes and inhibiting apoptosis.