Mesenchymal Stem Cell-Derived Exosome-Loaded microRNA-129-5p Inhibits TRAF3 Expression to Alleviate Apoptosis and Oxidative Stress in Heart Failure.

Heart failure (HF) represents a main global healthy and economic burden with unacceptably high morbidity and mortality rates. In the current study, we evaluated the potential effect of mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) on oxygen-glucose deprivation (OGD)-induced damages to HL-1 cells and HF mice and searched for the possible mechanism. MSC-Exos ameliorated oxidative stress and reduced apoptosis in OGD-treated HL-1 cells. By microarray analysis, we found that MSC-Exos treatment significantly increased the microRNA (miR)-129-5p expression in HL-1 cells. miR-129-5p inhibitor attenuated the protective effect of MSC-Exos on OGD-treated HL-1 cells. miR-129-5p targeted tumor necrosis factor receptor-associated factor 3 (TRAF3), and TRAF3 loss reversed the effect of miR-129-5p inhibitor by blunting the NF-κB signaling. MSC-Exos injection alleviated ventricular dysfunction and suppressed oxidative stress, apoptosis, inflammation, and fibrosis in cardiomyocytes in mice with HF by inhibiting NF-κB signaling pathway through miR-129-5p/TRAF3. Our findings suggest that exosomal miR-129-5p from MSCs protects the heart from failure by targeting TRAF3 and the following NF-κB signaling. This regulatory axis may be a possible therapeutic target for HF.