Unknown

Dataset Information

0

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 ER?. In endothelial cells, 27HC is also proadhesive via ER?, and in contrast to estrogen, which blunts NF-?B activation, 27HC stimulates NF-?B activation via Erk1,2 and JNK-dependent I?B? degradation. Whereas 27HC administration to apoe(-/-) mice increases atherosclerosis, apoe(-/-);er?(-/-) are unaffected. Thus, 27HC promotes atherosclerosis via proinflammatory processes mediated by ER?, and it attenuates estrogen-related atheroprotection. Strategies to lower 27HC may complement approaches targeting cholesterol to prevent vascular disease.

SUBMITTER: Umetani M 

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

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Umetani Michihisa M   Ghosh Pritam P   Ishikawa Tomonori T   Umetani Junko J   Ahmed Mohamed M   Mineo Chieko C   Shaul Philip W PW  

Cell metabolism 20140619 1


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 i  ...[more]

Similar Datasets

| S-EPMC6635382 | biostudies-literature
| S-EPMC7416714 | biostudies-literature
| S-EPMC5636879 | biostudies-other
| S-EPMC2194632 | biostudies-literature
2013-08-01 | E-GEOD-46924 | biostudies-arrayexpress
| S-EPMC3031608 | biostudies-literature
2021-06-16 | GSE171949 | GEO
2023-09-21 | GSE232895 | GEO
| S-ECPF-GEOD-46924 | biostudies-other
2013-08-01 | GSE46924 | GEO