Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the HAND2-AS1/miR-17-5p/Mfn2 axis.

BACKGROUND: The exosomes (exos) of bone marrow mesenchymal stem cells (BMSCs) play an important therapeutic role in repairing myocardial injury. The purpose of this study was to explore how the exos of BMSCs can alleviate the myocardial cell injury caused by hypoxia/reoxygenation (H/R) through HAND2-AS1/miR-17-5p/Mfn 2 pathway. METHODS: Cardiomyocytes H9c2 were damaged by H/R to mimic myocardial damage. Exos were gained from BMSC. The content of HAND2-AS1 and miR-17-5p was assessed by RT-qPCR. Cell survival rate and apoptosis were estimated by MTT assay and flow cytometry. Western blotting was used to detect the expression of protein. The contents of LDH, SOD, and MDA in the cell culture were detected by commercial kits. The luciferase reporter gene method confirmed the targeted relationships. RESULTS: In H9c2 cells induced by H/R, the level of HAND2-AS1 declined and the expression of miR-17-5p was elevated, but their expression was reversed after exo treatment. Exos improved the cell viability, declined cell apoptosis, controlled the oxidative stress, and repressed inflammation, thus attenuating the damage of H9c2 induced by H/R, whereas, the knockdown of HAND2-AS1 partly alleviated the impacts of exos. MiR-17-5p played the opposite role to HAND2-AS1 on H/R-injured myocardial cells. CONCLUSION: Exos derived from BMSC could alleviate H/R-induced myocardial injury by activating HAND2-AS1/miR-17-5p/Mfn2 pathway.