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Vascular Endothelial Estrogen Receptor Is Modulated by Estrogen Status and Related to Endothelial Function and Endothelial Nitric Oxide Synthase in Healthy Women

Department of Integrative Physiology (K.M.G., D.R.S., A.E.S., K.L.M.), University of Colorado at Boulder, Boulder, Colorado 80309; and Division of Geriatric Medicine (K.M.G., D.R.S., K.L.M.), Department of Medicine, University of Colorado Denver, Aurora, Colorado 80045

Address all correspondence and requests for reprints to: Kerrie Moreau, Ph.D., Assistant Professor of Medicine, Division of Geriatric Medicine, University of Colorado Denver, Building L15, Room 8111, 12631 East 17th Avenue, P.O. Box 6511, Aurora, Colorado 80045. E-mail: Kerrie.Moreau{at}ucdenver.edu.

Context and Objective: Estrogen receptor (ER), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ER is influenced by estrogen status and is related to vascular endothelial function in healthy women.

Methods: ER protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women.

Results: In premenopausal women (n = 10), ER expression was 30% lower (P < 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ER expression was 33% lower (P < 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ER expression was strongly related (r = 0.67; P < 0.001) to EDD, which was reduced in postmenopausal women. ER abundance was positively related to expression of eNOS (r = 0.54; P = 0.009; n = 21) and ser1177 phosphorylated eNOS (r = 0.59; P = 0.006; n = 20).

Conclusions: These results provide the first evidence that expression of ER in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ER expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.