PHENOTYPIC SWITCHING OF VASCULAR SMOOTH MUSCLE CELLS: KEY MECHANISM IN ATHEROSCLEROSIS PROGRESSION

Abstract

Vascular smooth muscle cells (VSMCs) have emerged as key contributors to atherosclerosis through their remarkable phenotypic plasticity. In response to vascular injury, inflammation, and metabolic stress, VSMCs transition from a differentiated contractile phenotype to a synthetic, proliferative, and migratory state. Recent evidence reveals that VSMCs also transdifferentiate into macrophage-like, osteogenic, and mesenchymal-like phenotypes, actively shaping plaque composition and stability. This review provides a comprehensive analysis of the molecular mechanisms underlying VSMC phenotypic modulation, including PDGF-BB, TGF-β, KLF4, TCF21, and non-coding RNAs. We also explore the dual roles of VSMCs in promoting vascular repair and contributing to disease progression. Understanding these processes offers novel insights into plaque pathobiology and presents promising therapeutic targets to stabilize atherosclerotic lesions and prevent adverse cardiovascular events.