FOXO1 Integrates Endothelial Hemodynamic, Inflammatory, and Metabolic Pathways in Atherosclerosis - PubMed
5 hours ago
- #endothelial cells
- #FOXO1
- #atherosclerosis
- Atherosclerosis occurs preferentially in regions with disturbed fluid shear stress (FSS), while physiological laminar FSS protects against it by suppressing endothelial inflammation.
- FOXO1 (forkhead box protein O1) integrates endothelial hemodynamic, inflammatory, and metabolic pathways in atherosclerosis.
- Oscillatory FSS and inflammatory cytokines induce FOXO1 nuclear translocation, whereas physiological FSS inhibits it via a KLF2-CDK2 pathway.
- Endothelial cell-specific deletion of FOXO1 reduces atherosclerotic plaques in hyperlipidemic mice.
- Glycolysis inhibition blocks oscillatory shear stress-induced FOXO1 nuclear translocation, while lactate promotes it via lactylation involving AARS1.
- Physiological FSS suppresses FOXO1 through KLF2-CDK2 signaling, suggesting potential therapeutic targets for atherosclerosis.