Vein graft failure after coronary artery bypass grafting (CABG) is primarily caused by intimal hyperplasia, which results from the phenotypic switching of venous smooth muscle cells (SMCs). This study investigates the role and underlying mechanism of miR-16-5p in the phenotypic switching of venous SMCs. In rats, neointimal thickness and area increased over time within 28 days after CABG, as did the time-dependent miR-16-5p downregulation and SMC phenotypic switching. Platelet-derived growth factor-BB-induced miR-16-5p downregulation in HSVSMCs was accompanied by and substantially linked with alterations in phenotypic switching indicators. Furthermore, miR-16-5p overexpression increased SMCs differentiation marker expression while suppressing HSVSMCs proliferation and migration and drastically inhibiting neointimal development in vein grafts. The miR-16-5p inhibited zyxin expression, which was necessary for HSVSMCs phenotypic switching. The miR-16-5p/zyxin axis is a novel, potentially therapeutic target for preventing and treating venous graft intimal hyperplasia.
Graphical abstract
Mounting evidence suggests that the phenotypic transformation of venous smooth muscle cells (SMCs) from differentiated (contractile) to dedifferentiated (proliferative and migratory) phenotypes causes excessive proliferation and further migration to the intima leading to intimal hyperplasia, which represents one of the key pathophysiological mechanisms of vein graft restenosis. In recent years, numerous miRNAs have been identified as specific phenotypic regulators of vascular SMCs (VSMCs), which play a vital role in intimal hyperplasia in vein grafts. The review sought to provide a comprehensive overview of the etiology of intimal hyperplasia, factors affecting the phenotypic transformation of VSMCs in vein graft, and molecular mechanisms of miRNAs involved in SMCs phenotypic modulation in intimal hyperplasia of vein graft reported in recent years.
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