Upregulation of miR-126-3p promotes human saphenous vein endothelial cell proliferation in vitro and prevents vein graft neointimal formation ex vivo and in vivo
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Qingxi Qu1, Weidong Bing1, Xiangbin Meng1, Jie Xi1, Xiao Bai1, Qing Liu2, Yaqiu Guo3, Xin Zhao1 and Yanwen Bi1
1Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
2Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, China
3Department of Anesthesiology, Jinan Maternity and Child Health Care Hospital, Jinan, Shandong 250012, China
Yanwen Bi, email: [email protected]
Keywords: miRNAs, human saphenous vein, vein graft, endothelial cells, neointimal formation
Received: June 30, 2017 Accepted: August 27, 2017 Published: November 03, 2017
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 in vitro 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) ex vivo. 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.
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