Extracellular vesicles derived from HBMSCs improved myocardial infarction through inhibiting zinc finger antisense 1 and activating Akt/Nrf2/HO-1 pathway.

Myocardial infarction (MI) is believed to be one of the most common cardiovascular diseases, and it is seriously threatening the health of people in the world. The extracellular vesicles (EVs) isolated from mesenchymal stem cells and zinc finger antisense 1 (ZFAS1) have been believed to be involved in the regulation of MI, but the mechanism has not been fully clarified. Left anterior descending artery ligation was used to establish MI animal model, hypoxia treatment was applied to establish MI cell model. CCK8, transwell, and wound healing methods were applied to measure cell proliferation, invasion, and migration. Overexpression of ZFAS1 was established via transfecting pcDNA-ZFAS1. Overexpression of ZFAS1 significantly reversed the influence of EVs on cell migration, invasion, and apoptosis. Similar effect of EVs and ZFAS1 on morphological changes of MI rat heart tissues were also observed. The activation of Akt/Nrf2/HO-1 pathway by EVs was remarkably suppressed by pcDNA-ZFAS1. Inhibitor of Akt/Nrf2/HO-1 pathway remarkably reversed the impact of EVs on the cell viability. EVs might improve MI through inhibiting ZFAS1 and promoting Akt/Nrf2/HO-1 pathway. This study might provide a new thought for the prevention and treatment of MI damage through regulating ZFAS1 or Akt/Nrf2/HO-1 pathway.