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27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen.

Abstract：

:The cardioprotective effects of estrogen are mediated by receptors expressed in vascular cells. Here we show that 27-hydroxycholesterol (27HC), an abundant cholesterol metabolite that is elevated with hypercholesterolemia and found in atherosclerotic lesions, is a competitive antagonist of estrogen receptor action in the vasculature. 27HC inhibited both the transcription-mediated and the non-transcription-mediated estrogen-dependent production of nitric oxide by vascular cells, resulting in reduced estrogen-induced vasorelaxation of rat aorta. Furthermore, increasing 27HC levels in mice by diet-induced hypercholesterolemia, pharmacologic administration or genetic manipulation (by knocking out the gene encoding the catabolic enzyme CYP7B1) decreased estrogen-dependent expression of vascular nitric oxide synthase and repressed carotid artery reendothelialization. As well as antiestrogenic effects, there were proestrogenic actions of 27HC that were cell-type specific, indicating that 27HC functions as an endogenous selective estrogen receptor modulator (SERM). Taken together, these studies point to 27HC as a contributing factor in the loss of estrogen protection from vascular disease.

journal_name

Nat Med

journal_title

Nature medicine

authors

Umetani M,Domoto H,Gormley AK,Yuhanna IS,Cummins CL,Javitt NB,Korach KS,Shaul PW,Mangelsdorf DJ

doi

10.1038/nm1641

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

1185-92

issue

10

eissn

1078-8956

issn

1546-170X

pii

nm1641

journal_volume

13

pub_type

杂志文章

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