microRNA‐129 overexpression in endothelial cell‐derived extracellular vesicle influences inflammatory response caused by myocardial ischemia/reperfusion injury

Abstract

Extracellular vesicles (EVs) have the potency to function as modulators in the process of myocardial ischemia/reperfusion (I/R) injury. This investigation was performed to decipher the mechanism of human umbilical vascular endothelial cells (HUVECs)‐derived EVs in myocardial I/R injury with the involvement of microRNA‐129 (miR‐129). HUVECs‐secreted EVs were collected and identified. An I/R mouse model was developed, and cardiomyocytes were used for vitro oxygen‐glucose deprivation/reperfusion model establishment. Differentially expressed miRNAs in myocardial tissues after EV treatment were assessed using microarray analysis. The target relationship between miR‐129 and toll‐like receptor 4 (TLR4) was identified using a dual‐luciferase assay. Gain‐ and loss‐function studies regarding miR‐129 were implemented to figure out its roles in myocardial I/R injury. Meanwhile, the activation of the nuclear factor‐kappa‐binding (NF‐κB) p65 signaling and NOD‐like receptor 3 (NLRP3) inflammasome was evaluated. EVs diminished the apoptosis of cardiomyocytes and the secretion of inflammatory factors, and all these trends were reversed by miR‐129 reduction. miR‐129 bound to the 3′‐untranslated region of TLR4 directly. The NF‐κB p65 signaling and NLRP3 inflammasome were abnormally activated after I/R injury, whose impairment after EVs was partially restored by miR‐129 downregulation. This study illustrated that EVs could carry miR‐129 to mitigate myocardial I/R injury via downregulating TLR4 and disrupting the NF‐κB signaling and NLRP3 inflammasome.