Premature cell senescence promotes vascular smooth muscle cell phenotypic modulation and resistance to re-differentiation.

ABSTRACT:

Aims

Human atherosclerotic plaque cells display DNA damage that if left unrepaired can promote premature cell senescence. Vascular smooth muscle cells (VSMCs) predisposed to senescence promote atherogenesis and features of unstable plaques and increase neointima formation after injury. However, how premature VSMC senescence promotes vascular disease and its effects on VSMC phenotype are unknown.

Methods and results

Bulk RNA-seq of primary human VSMCs identified 126 significantly up- or down-regulated genes after both DNA damage-induced (D + R) or replicative senescence (RS). Up-regulated genes included senescence markers CDKN2A (p16) and ICAM1 and genes expressed by phenotypically modulated de-differentiated/'fibromyocytic' VSMCs [osteoprotegerin (TNFRSF11B), fibromodulin (F

SUBMITTER: Kaistha A 

PROVIDER: S-EPMC12352304 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature