Abstract
Introduction: Acute Myocardial Infarction (AMI) has been classified as a prevalent condition threatening human health. This study sought to explore the effects of bone marrow mesenchymal stem cells (BMSCs)-extracellular vesicles (EVs) on cardiomyocyte apoptosis and autophagy induced by ischemia- hypoxia (I/H).
Materials and Methods: EVs were isolated from BMSCs using ultracentrifugation. The I/H cardiomyocyte model was established and cultured with EVs to evaluate the internalization of EVs by the cardiomyocyte line, apoptosis, proliferation, and autophagy of the cardiomyocyte line. The targeting relationship between miR-144-3p and ROCK1 was verified. EVs were isolated after transfection of BMSCs with the miR-144-3p inhibitor to evaluate the effect of miR-144-3p on the cardiomyocyte line.
Results and Discussion: After overexpression of ROCK1 in the I/H cardiomyocyte line treated with EVs, the I/H cardiomyocyte line apoptosis and autophagy were determined. BMSCs-EVs suppressed I/Hinduced apoptosis and autophagy of the cardiomyocyte line. BMSCs-EVs carried miR-144-3p into the I/H cardiomyocyte line, and the down-regulation of miR-144-3p in EVs partially inverted the suppression of apoptosis and autophagy of the I/H cardiomyocyte line induced by EVs. Our findings denoted that miR- 144-3p targeted ROCK1. Overexpression of ROCK1 partially inverted the inhibition of EVs on I/H cardiomyocyte line apoptosis and autophagy. BMSCs-EVs-derived miR-144-3p targeted ROCK1 to radically activate the PI3K/AKT/mTOR pathway.
Conclusion: Overall, our study elicited that BMSCs-EVs carried miR-144-3p into the I/H cardiomyocyte line to target ROCK1 and stimulate the PI3K/AKT/mTOR pathway, thus inhibiting I/H-induced cardiomyocyte line apoptosis and autophagy.
Keywords: Bone marrow mesenchymal stem cells, Extracellular vesicles, AC16, miR-144-3p, ROCK1, Apoptosis, Autophagy, PI3K/AKT/mTOR
Graphical Abstract
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