Exosomes derived from miR‐146a‐modified adipose‐derived stem cells attenuate acute myocardial infarction?induced myocardial damage via downregulation of early growth response factor 1 Exosomes derived from miR‐146a‐modified adipose‐derived stem cells attenuate acute myocardial infarction?induced myocardial damage via downregulation of early growth response factor 1

摘要

Abstract Multiple studies demonstrated that early growth response factor 1 (EGR1) induces myocardial damage after acute myocardial infarction (AMI). Recent evidence indicates that microRNAs (miRNA) play an important role in exosome‐mediated cardioprotection after AMI. Bioinformatics analysis has shown that miR‐146a can regulate the expression of EGR1, so the aim of this study was to determine if miR‐146a plays a role in exosome‐mediated cardioprotection by regulation of EGR1 after AMI. Exosomes were isolated from wild‐ or miR‐146a‐modified adipose‐derived stem cells (ADSCs), and the therapeutic effect of exosomes was assessed in an AMI model in rats and hypoxic‐induced H9c2 model cells. The results showed that miR‐146a containing exosomes had more effect than the exosome treatment group on the suppression of AMI‐induced apoptosis, inflammatory response, and fibrosis in an AMI rat model. Both in vivo and in vitro experiments found that miR‐146a interacted with the 3′‐untranslated region of EGR1 and suppressed posttranscriptional EGR1 expression, which was confirmed by the luciferase reporter assay. We also found that suppressed EGR1 expression reversed AMI or hypoxia‐induced TLR4/NFκB signal activation, which played an important role in the promotion of myocardial cell apoptosis, inflammatory response, and fibrosis. Taken together, these findings suggested that exosomes derived from miR‐146a‐modified ADSCs attenuated AMI‐induced myocardial damage via downregulation of EGR1.