Human bone marrow mesenchymal stem cell–derived extracellular vesicles enriched with miR-146a attenuate myocardial ischemia–reperfusion injury via suppression of inflammatory and oxidative stress pathways

miR-146a evs attenuate myocardial I/R injury

Abstract

This study aims to evaluate the cardioprotective properties of miR-146a-enriched Extracellular vesicles (EV) derived from human bone-marrow mesenchymal stem cells (MSCs) (BMSCs). BMSCs were transfected with miR-146a mimics or control mimics, and the EVs were isolated.  Thirty Sprague-Dawley male rats were randomly divided into myocardial I/R Control, I/R + EV control, and I/R + miR-146a EVs groups, and EVs were administered intravenously at the time of reperfusion. Afterward, plasma cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), TNF-α, IL-6, and IL-1β were measured using ELISA, and IRAK1, TRAF6, NF-κB1, NLRP3, Caspase 1, IL-1β, Nox2, and Nox4 were evaluated in left ventricular tissue by RT-PCR. Results indicated that the miR-146a-enriched EVs reduced plasma levels of cTnI, CK-MB, and MDA, and increased plasma levels of SOD and GSH-Px compared with the control groups. Levels of TNF-α, IL-6, and IL-1β were also significantly reduced. RT-qPCR further showed that TRAF6 and NF-κB1 were downregulated, with decreased transcription of NLRP3, Caspase 1, IL-1β, and oxidative stress markers Nox2 and Nox4. MSC-derived EVs enriched with miR-146a can reduce myocardial I/R injury in rats by inhibiting inflammatory and oxidative-stress pathways via inhibition of the TRAF6/NF-κB/NLRP3 axis.