MicroRNA-342-3p lOaded by Human Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Attenuates Deep Vein Thrombosis by Downregulating EDNRA Running Title: Exosome Delivery of miR-342-3p in DVT

Abstract

Objective: Exosomes (exos) exert biological functions to maintain the dynamic balance of cells and tissues by transferring biological cargo to recipient cells. Thus, this study explored human umbilical cord mesenchymal stem cells (hucMSCs)-derived exo transfer of microRNA (miR)-342-3p in deep vein thrombosis (DVT).Methods: HucMSCs were isolated and transfected with miR-342-3p antagomir/agomir. Then, hucMSCs-exos were extracted and injected into rats with DVT to observe inflammation and pathological damage in thrombotic vein. HucMSCs-exos were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro to observe angiogenesis. miR-342-3p and endothelin A receptor (EDNRA) expression in rats with DVT, as well as their interaction was analyzed.Results: miR-342-3p was downregulated and EDNRA was upregulated in rats with DVT. HucMSCs-exos induced the repair of venous thrombosis and suppressed inflammation and pathological injury in rats with DVT, as well as promoted angiogenesis of HUVECs. Upregulated miR-342-3p delivery by hucMSCs-exos alleviated DVT in rats and improved angiogenesis of HUVECs, while downregulated miR-342-3p performed oppositely. miR-342-3p targeted EDNRA, and the effect of hucMSCs-exos transfer of upregulated miR-342-3p was rescued by overexpressing EDNRA.Conclusion: Briefly, miR-342-3p loaded by hucMSCs-exos attenuates DVT by downregulating EDNRA, offering a novel direction to treat DVT.