Poly(ADP-ribose) polymerase 1 orchestrates vascular smooth muscle cell homeostasis in arterial disease.

ABSTRACT: Smooth muscle cells are remarkably plastic. Their reversible differentiation is required for growth and wound healing but also contributes to pathologies such as atherosclerosis and restenosis. Here we demonstrate the role of poly(ADP-ribose) polymerase 1 (PARP1) as a critical master regulator of vascular smooth muscle cells (VSMC) plasticity. A robust activation of PARP1 in VSMCs was observed in artery stenosis and atherosclerotic plaques of rodents and human. Inhibition or deletion of PARP1 suppressed the VSMC phenotype switch in vivo and in vitro. Further analysis identified myocardin and myocardin-associated serum response factor as substrates of PARP1-mediated poly(ADP-ribosyl)ation reaction. Poly(ADP-ribosyl)ation of myocardin and serum response factor dissociated the complex from CA

SUBMITTER: Xu W 

PROVIDER: S-EPMC12411612 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature