Phenotypic switching of vascular smooth muscle cells: a central mechanism in vein graft intimal hyperplasia

Coronary artery bypass grafting (CABG) remains the cornerstone of revascularization for patients with complex coronary artery disease. While the great saphenous vein (GSV) is the most widely used conduit, its long-term patency is limited by postoperative intimal hyperplasia (IH) and accelerated atherosclerosis. Central to this pathological process is the phenotypic switching of vascular smooth muscle cells (VSMCs) from a quiescent contractile state to a proliferative, migratory, and synthetic phenotype. This review systematically summarizes the structural and functional differences between venous and arterial grafts, the sequential pathological mechanisms of vein graft failure, and the molecular drivers of VSMCs phenotypic switching. Key regulatory pathways-including PDGF-BB, TGF-β, MAPK, mTOR, and NF-κB-as well as non-coding RNAs, orchestrate this process in response to endothelial dysfunction, inflammatory activation, and altered hemodynamics. In addition, emerging therapeutic strategies aimed at mitigating IH are discussed, including optimized surgical harvesting techniques, improved conduit preservation solutions, pharmacological agents, gene therapy, and venous external stenting. Despite significant advances, the complexity of VSMCs regulatory networks and the limitations of current interventions underscore the need for integrative approaches combining molecular targeting with innovative delivery systems. Elucidating these mechanisms holds promise for enhancing long-term vein graft patency and improving outcomes in patients undergoing CABG.