LATS1/2-CD38 Metabolic Rewiring Links Senescence to Intraplaque Thrombosis - PubMed
3 hours ago
- #metabolic reprogramming
- #intraplaque thrombosis
- #endothelial cells
- The study explores how LATS1/2 loss in endothelial cells under disturbed blood flow links to intraplaque thrombosis via metabolic reprogramming.
- Using EC-specific knockout mice, researchers found that loss of LATS1/2 induces a senescence-associated stemness phenotype driven by CD38 upregulation.
- Spatial multiomics revealed CD38 suppresses SUOX, leading to sulfite accumulation, altered mitochondrial metabolism, and increased ATP consumption despite energy stress.
- This metabolic rewiring promotes EC proliferation and senescence, resulting in fragile neovessels and intraplaque thrombosis, which can be mitigated by CD38 inhibition.
- Similar findings in human plaques suggest the mechanism is relevant to atherothrombosis in acute coronary syndromes.