Methoxyestradiols mediate the antimitogenic effects of estradiol on vascular smooth muscle cells via estrogen receptor-independent mechanisms.

Authors: Dubey, RK  Gillespie, DG  Zacharia, LC  Rosselli, M  Korzekwa, KR  Fingerle, J  Jackson, EK 
Citation: Dubey RK, etal., Biochem Biophys Res Commun. 2000 Nov 11;278(1):27-33.
Pubmed: (View Article at PubMed) PMID:11071850
DOI: Full-text: DOI:10.1006/bbrc.2000.3755

Estrogen receptors (ERs) are widely held to mediate the ability of 17 beta-estradiol (estradiol) to attenuate injury-induced proliferation of vascular smooth muscle cells (VSMCs) leading to vascular lesions. However, recent findings that estradiol prevents injury-induced vascular lesion formation in knock-out mice lacking either ER alpha or ER beta seriously challenge this concept. Here we report that the local metabolism of estradiol to methoxyestradiols, endogenous metabolites of estradiol with no affinity for ERs, is responsible for the ER-independent inhibitory effects of locally applied estradiol on rat VSMC growth. These finding imply that local vascular estradiol metabolism may be an important determinant of the cardiovascular protective effects of circulating estradiol. Thus, interindividual differences, either genetic or acquired, in the vascular metabolism of estradiol may define a given female's risk of cardiovascular disease and influence the cardiovascular benefit she receives from estradiol replacement therapy in the postmenopausal state. These findings also imply that nonfeminizing estradiol metabolites may confer cardiovascular protection in both women and men.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 2289790
Created: 2008-02-11
Species: All species
Last Modified: 2008-02-11
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.