Upregulation of miR-126-3p promotes human saphenous vein endothelial cell proliferation <i>in vitro</i> and prevents vein graft neointimal formation <i>ex vivo</i> and <i>in vivo</i>

Abstract

Poor long-term patency of vein grafts remains an obstacle in coronary artery bypass grafting (CABG) surgery using an autologous saphenous vein graft. Recent studies have revealed that miR-126-3p promotes vascular integrity and angiogenesis. We aimed to identify the role of miR-126-3p in the setting of vein graft disease and investigate the value of miR-126-3p agomir as a future gene therapy in vein graft failure. Expression analysis of circulating miR-126-3p in plasma from CABG patients established the basic clues that miR-126-3p participates in CABG. The <i>in vitro</i> results indicated that elevated miR-126-3p expression significantly improved proliferation and migration in human saphenous vein endothelial cells (HSVECs) by targeting sprouty-related protein-1 (SPRED-1) and phosphatidylinositol-3-kinase regulatory subunit 2 (PIK3R2), but not in human saphenous vein smooth muscle cells (HSVSMCs). Moreover, the therapeutic potential of miR-126-3p agomir was demonstrated in cultured human saphenous vein (HSV) <i>ex vivo</i>. Finally, local delivery of miR-126-3p agomir was confirmed to enhance reendothelialization and attenuate neointimal formation in a rat vein arterialization model. In conclusion, we provide evidence that upregulation of miR-126-3p by agomir possesses potential clinical value in the prevention and treatment of autologous vein graft restenosis in CABG.