Estrogen receptors (ERs) are widely held to mediate the ability of 17β-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 knockout mice lacking either ERα or ERβ 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. (C) 2000 Academic Press.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 11 Nov 2000|
- Cardiovascular disease
- Hormone replacement therapy
- Vascular remodeling