PRDM16 regulates smooth muscle cell identity and atherosclerotic plaque composition

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 fibrou...

Full description

Saved in:
Bibliographic Details
Published in:Nature cardiovascular research Vol. 4; no. 11; p. 1573
Main Authors: Tan, Josephine M E, Cheng, Lan, Calhoun, Ryan P, Weller, Angela H, Drareni, Karima, Fong, Skylar, Barbara, Eirlys, Lim, Hee-Woong, Xue, Chenyi, Winter, Hanna, Auguste, Gaëlle, Miller, Clint L, Reilly, Muredach P, Maegdefessel, Lars, Lutgens, Esther, Seale, Patrick
Format: Journal Article
Language:English
Published: England 01.11.2025
Subjects:
Animals
Atherosclerosis - genetics
Atherosclerosis - metabolism
Atherosclerosis - pathology
Cell Movement
Cell Proliferation
Cells, Cultured
Disease Models, Animal
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Fibrosis
Foam Cells - metabolism
Foam Cells - pathology
Gene Expression Regulation
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - pathology
Myocytes, Smooth Muscle - metabolism
Myocytes, Smooth Muscle - pathology
Phenotype
Plaque, Atherosclerotic
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - metabolism
ISSN:2731-0590, 2731-0590
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 and fewer foam cells. Conversely, enforced PRDM16 expression suppressed SMC migration, proliferation and fibrosis. Mechanistically, PRDM16 occupied chromatin and suppressed activating marks at synthetic loci. These findings establish PRDM16 as a gatekeeper of SMC fate and reveal its role in shaping atherosclerotic plaque composition.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2731-0590
2731-0590
DOI:10.1038/s44161-025-00737-8