Beyond a Simple Switch: Decoding the Multifactorial Phenotypic Plasticity of Vascular Smooth Muscle Cells

Vascular smooth muscle cells (VSMCs) are central to the maintenance of vascular homeostasis and the progression of cardiovascular diseases (CVDs), owing to their remarkable phenotypic plasticity. This editorial introduces a Special Issue of Cells that compiles recent advances in our understanding of the molecular, epigenetic, metabolic, and mechanical mechanisms that govern VSMC behavior. Highlighted contributions explore the roles of RNA modifications, chromatin remodeling, lipid metabolism, and mechanotransduction in VSMC phenotypic switching, revealing new therapeutic targets and diagnostic opportunities. Together, these studies emphasize the multifactorial regulation of VSMC plasticity and its dual role in vascular repair and disease pathogenesis.