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

Abstract

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:ERproteinexpressionwasmeasured(quantitativeimmunofluorescence)inendothelial cellsfromperipheralveinsof16healthy,premenopausalwomenduringtheearlyfollicular(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 endothelialnitricoxidesynthase(eNOS)expressionandactivationwerealsomeasuredinasubgroupof 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 postmenopausalwomen,ERexpressionwas33%lower(P0.001)comparedwiththeLFphaseofthe menstrualcycleinpremenopausalwomen.ERexpressionwasstronglyrelated(r0.67;P0.001) 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).