Vascular Pharmacology · Oct 22, 2026
Epigenetic regulation of vascular smooth muscle cell plasticity in vascular injury, repair, and aging
By Zheng XL, Sun J, Yin H et al.
Vascular smooth muscle cells (VSMCs) exhibit a remarkable phenotypic spectrum in response to injury, inflammation, metabolic stress, and aging through state changes encoded in chromatin. This review examines how DNA methylation and hydroxymethylation, histone modifiers, chromatin readers, adenosine triphosphate (ATP)-dependent chromatin remodelers, three-dimensional genome organization, and non-coding RNAs (ncRNAs) shape VSMC plasticity in intimal hyperplasia, atherosclerosis and vascular aging. Bromodomain-containing protein 4 (BRD4) is used as a case study because it links acetyl-lysine recognition to transcriptional programs and BRD4 inhibition has been reported to affect VSMC biology in vivo. Based on published evidence, we discuss the timing and delivery of potential vascular epigenetic targeting: short-term, local chromatin-directed therapy may help restrain maladaptive VSMC proliferation after acute artery injury, whereas chronic conditions, including atherosclerosis and vascular aging, would require careful long-term dosing that preserves endothelial repair, VSMC contractile state and hematopoietic safety. These therapeutic implications remain preclinical hypotheses, with clinical efficacy remaining to be established.