PRDM16 regulates smooth muscle cell identity and atherosclerotic plaque composition.

ABSTRACT: Vascular smooth muscle cells (SMCs) undergo phenotype switching to acquire various fates in response to pathological stimuli. Among these, 'synthetic' SMCs-defined by migration, proliferation and extracellular matrix production-accumulate in atherosclerotic lesions and contribute to fibrous cap formation. The mechanisms driving this synthetic transition remain unclear. Here we identify PRDM16, a gene linked to cardiovascular disease, as a critical transcriptional repressor of the synthetic SMC phenotype. PRDM16 expression declined during SMC modulation, and its deletion in mice induced a synthetic program across all SMC subtypes even without pathological stimuli. Under atherogenic conditions, PRDM16 deficiency resulted in the formation of fibroproliferative plaques with more synthetic SMCs

SUBMITTER: Tan JME 

PROVIDER: S-EPMC12611775 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature