Vascular smooth muscle cell proliferation and migration pathways (VSMC proliferation and migration)

Vascular smooth muscle cell (VSMC) proliferation and migration pathways represent the integrated signaling networks that control the transition of VSMCs from a quiescent, contractile phenotype to an active, synthetic phenotype (Bennett et al., 2016, Circulation Research). Under physiological conditions, VSMCs maintain vascular tone, but in response to injury or inflammation, they proliferate and migrate into the subendothelial space (Louis and Zahradka, 2010, Canadian Journal of Physiology and Pharmacology). This process is primarily driven by growth factors such as Platelet-Derived Growth Factor (PDGF) and Fibroblast Growth Factor (FGF), which activate downstream cascades like the MAPK/ERK and PI3K/Akt/mTOR pathways (Raines, 2004, Cytokine & Growth Factor Reviews). Pathological activation of these pathways is a central mechanism in the development of atherosclerosis, hypertension, and neointimal hyperplasia following vascular interventions (Durham et al., 2018, Nature Reviews Cardiology). Therapeutic strategies, such as drug-eluting stents (DES), utilize agents like Sirolimus or Paclitaxel to locally inhibit these pathways and prevent restenosis (Ali et al., 2016, JACC). However, non-selective inhibition can impair re-endothelialization, increasing the risk of late stent thrombosis (Jonsson et al., 2001, Catheterization and Cardiovascular Interventions). Consequently, these pathways are critical focal points for cardiovascular drug development and precision medicine.

Other names

VSMC phenotypic switchingVascular remodeling pathwaysNeointimal hyperplasia pathwaysSmooth muscle cell migration and proliferation

Drugs targeting these pathways generally function by inhibiting key regulatory nodes such as the mammalian target of rapamycin (mTOR), stabilizing microtubules to induce cell cycle arrest, or blocking receptor tyrosine kinases like Platelet-Derived Growth Factor (PDGF) receptor to prevent the initiation of the proliferative and migratory response (Ali et al., 2016, JACC; Raines, 2004, Cytokine & Growth Factor Reviews).