The cholesterol metabolite 27-hydroxycholesterol promotes atherosclerosis via proinflammatory processes mediated by estrogen receptor alpha.

ABSTRACT: Oxysterols are cholesterol metabolites that serve multiple functions in lipid metabolism, including as liver X receptor (LXR) ligands. 27-hydroxycholesterol (27HC) is an abundant oxysterol metabolized by CYP7B1. How 27HC impacts vascular health is unknown. We show that elevations in 27HC via cyp7b1 deletion promote atherosclerosis in apoe(-/-) mice without altering lipid status; furthermore, estrogen-related atheroprotection is attenuated. In wild-type mice, leukocyte-endothelial cell adhesion is increased by 27HC via estrogen receptor (ER)-dependent processes. In monocytes/macrophages, 27HC upregulates proinflammatory genes and increases adhesion via ERα. In endothelial cells, 27HC is also proadhesive via ERα, and in contrast to estrogen, which blunts NF-κB activation, 27HC stimulates NF-

SUBMITTER: Umetani M 

PROVIDER: S-EPMC4098728 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature