Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis

Background: The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stromal cells (MSCs) have the ability to improve Myocardial infarction (MI). Some microRNAs (miRNAs) including miR-497 and related target genes have been proved to be closely linked with heart diseases. However, EVs could regulate MI process through miR-497, and the mechanisms have not been fully reported. Methods: Ligation of left anterior descending artery was performed to established MI animals model. Hypoxia cell model was established through lowering the level of oxygen. The cell invasion, migration, and proliferation were measured using tanswell, wound healing, and MTT assays. HE, Masson trichrome, and Sirius Red staining were used to investigate the morphological changes. Results: Overexpression of miR-497 reversed the promotion of cell migration, invasion, and proliferation caused by EVs. The improvement of cardiac function induced by EVs could also be reversed by overexpression of miR497. Direct binding site between Smad7 and miR-497 was identified. Knockdown of Smad7 reversed the improvement of cardiac function induced by EVs. Conclusions: We found that EVs isolated from MSCs might improve the cardiac injury caused by MI through targeting miR497/Smad7. This study provides novel potential therapeutic thought for the prevention and treatment of MI through targeting miR-497/Smad7.