MSCs-Derived Extracellular Vesicles Carrying miR-212-5p Alleviate Myocardial Infarction-Induced Cardiac Fibrosis via NLRC5/VEGF/TGF-beta 1/SMAD Axis

The purpose of the present study was to define the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in the progression of myocardial infarction (MI)-induced cardiac fibrosis. An in vitro cell model of hypoxia-induced cardiac fibrosis was constructed in cardiac fibroblasts (CFs). miR-212-5p was poorly expressed in clinical pathological samples and animal models of cardiac fibrosis caused by MI, while miR-212-5p expression was enriched in EVs released from MSCs. EVs from MSCs were isolated, evaluated, and co-cultured with CFs. Dual-luciferase reporter gene assay revealed that miR-212-5p negatively targeted NLRC5 progression of cardiac fibrosis. Following loss- and gain-function assay, EVs expressing miR-212-5p protected against cardiac fibrosis evidenced by reduced levels of alpha-SMA, Collagen I, TGF-beta 1, and IL-1 beta. In vivo experiments further confirmed the above research results. Collectively, EVs from MSCs expressing miR-212-5p may attenuate MI by suppressing the NLRC5/VEGF/TGF-beta 1/SMAD axis.