MicroRNA‐365 promotes the contractile phenotype of venous smooth muscle cells and inhibits neointimal formation in rat vein grafts

• Published in: IUBMB life 2019-07, Vol.71 (7), p.908-916
• Main Authors: Cao, Bo‐Jun, Zhu, Lei, Wang, Xiao‐Wen, Zou, Rong‐Jiang, Lu, Zhi‐Qian
• Format: Article
• Language: English
• Subjects: Adenoviruses; Animals; Autografts; Cell Proliferation; Cells, Cultured; Cyclin D1; Gene expression; Gene Expression Profiling; Graft rejection; Hemodynamics; Hyperplasia; Jugular Veins - metabolism; Jugular Veins - transplantation; Male; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐365; Muscle Contraction; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - physiology; Neointima - genetics; Neointima - pathology; Neointima - prevention & control; neointimal formation; Phenotype; Phenotypes; Rats; Rats, Sprague-Dawley; Smooth muscle; Stents; Surgery; Transfection; Trypsin; Vascular Grafting - methods; vein graft failure; Veins & arteries; venous smooth muscle cell
• ISSN: 1521-6543; 1521-6551
• DOI: 10.1002/iub.2022

The high rate of autologous vein graft failure caused by neointimal hyperplasia remains an unresolved issue in the field of cardiovascular surgery; therefore, it is important to explore new methods for protecting against neointimal hyperplasia. MicroRNA‐365 has been reported to inhibit the proliferation of vascular smooth muscle cells (SMCs). This study aimed to test whether adenovirus‐mediated miR‐365 was able to attenuate neointimal formation in rat vein grafts. We found that miR‐365 expression was substantially reduced in vein grafts following engraftment. In vitro, overexpression of miR‐365 promoted smooth muscle‐specific gene expression and inhibited venous SMC proliferation and migration. Consistent with this, overexpression of miR‐365 in a rat vein graft model significantly reduced grafting‐induced neointimal formation and effectively improved the hemodynamics of the vein grafts. Mechanistically, we identified that cyclin D1 as a potential downstream target of miR‐365 in vein grafts. Specially, to increase the efficiency of miR‐365 gene transfection, a 30% poloxamer F‐127 gel containing 0.25% trypsin was mixed with adenovirus and spread around the vein grafts to increase the adenovirus contact time and penetration. We showed that adenovirus‐mediated miR‐365 attenuated venous SMC proliferation and migration in vitro and effectively inhibited neointimal formation in rat vein grafts. Restoring expression of miR‐365 is a potential therapeutic approach for the treatment of vein graft failure. © 2019 IUBMB Life, 2019