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Activation of Estrogen Receptor-&agr; Reduces Aortic Smooth Muscle Differentiation

Activation of Estrogen Receptor-&agr; Reduces Aortic Smooth Muscle Differentiation Activation of Estrogen Receptor- Reduces Aortic Smooth Muscle Differentiation Christine R. Montague, Melissa G. Hunter, Mikhail A. Gavrilin, Gary S. Phillips, Pascal J. Goldschmidt-Clermont, Clay B. Marsh Abstract—Women are at high risk of dying from unrecognized cardiovascular disease. Many differences in cardiovascular disease between men and women appear to be mediated by vascular smooth muscle cells (SMC). Because estrogen reduces the proliferation of SMC, we hypothesized that activation of estrogen receptor- (ER) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ER expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ER and higher levels of the differentiation markers calponin and smooth muscle -actin than SMC from women. When SMC containing low expression of ER were transduced with a lentivirus containing ER, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ER expression by small interfering RNA (siRNA) in cells expressing high levels of ER enhanced the expression of differentiation markers. ER expression and activation reduced the phosphorylation of Smad2, a signaling molecule important in differentiation of SMC and initiated cell http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Circulation Research Wolters Kluwer Health

Activation of Estrogen Receptor-&agr; Reduces Aortic Smooth Muscle Differentiation

Marsh, Clay B.
Circulation Research , Volume 99 (5) – Sep 1, 2006
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References (32)

ISSN
0009-7330
eISSN
1524-4571
DOI
10.1161/01.RES.0000238376.72592.a2
pmid
16873715
Publisher site
See Article on Publisher Site

Abstract

Activation of Estrogen Receptor- Reduces Aortic Smooth Muscle Differentiation Christine R. Montague, Melissa G. Hunter, Mikhail A. Gavrilin, Gary S. Phillips, Pascal J. Goldschmidt-Clermont, Clay B. Marsh Abstract—Women are at high risk of dying from unrecognized cardiovascular disease. Many differences in cardiovascular disease between men and women appear to be mediated by vascular smooth muscle cells (SMC). Because estrogen reduces the proliferation of SMC, we hypothesized that activation of estrogen receptor- (ER) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ER expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ER and higher levels of the differentiation markers calponin and smooth muscle -actin than SMC from women. When SMC containing low expression of ER were transduced with a lentivirus containing ER, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ER expression by small interfering RNA (siRNA) in cells expressing high levels of ER enhanced the expression of differentiation markers. ER expression and activation reduced the phosphorylation of Smad2, a signaling molecule important in differentiation of SMC and initiated cell

Journal

Circulation Research – Wolters Kluwer Health

Published: Sep 1, 2006

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