Sentrin-specific protease 3 (SENP3)-mediated Kruppel-like factor 4 (KLF4) deSUMOylation regulates vascular smooth muscle cell phenotypic switching in atherosclerosis.

ABSTRACT: Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile toward a synthetic phenotype plays a critical role in atherosclerosis. Although the redox-sensitive sentrin/Small Ubiquitin-like Modifier (SUMO)-specific protease 3 (SENP3), which preferentially deconjugates SUMO2/3, has been linked to oxidative stress, its role in atherosclerosis remains poorly defined. In this study, we demonstrate that SENP3 is significantly upregulated in human and mouse atherosclerotic lesions and in VSMCs exposed to pro-atherogenic stimuli. Using smooth muscle-specific Senp3 knockout mice (ApoE^-/-;Senp3^flox/flox;Tagln-Cre) and SENP3-knockdown VSMC models, we show that SENP3 deficiency preserves the contractile phenotype of VSMCs, suppresses their proliferation and mi

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12660617 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature