Activation of estrogen receptor-α reduces aortic smooth muscle differentiation

Christine R. Montague, Melissa G. Hunter, Mikhail A. Gavrilin, Gary S. Phillips, Pascal Goldschmidt-Clermont, Clay B. Marsh

Research output: Contribution to journalArticle

24 Citations (Scopus)

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-α (ERα) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ERα expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ERα and higher levels of the differentiation markers calponin and smooth muscle α-actin than SMC from women. When SMC containing low expression of ERα were transduced with a lentivirus containing ERα, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ERα expression by small interfering RNA (siRNA) in cells expressing high levels of ERα enhanced the expression of differentiation markers. ERα expression and activation reduced the phosphorylation of Smad2, a signaling molecule important in differentiation of SMC and initiated cell death through cleavage of caspase-3. We conclude that ERα activation switched SMC to a dedifferentiated phenotype and may contribute to plaque instability.

Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalCirculation Research
Volume99
Issue number5
DOIs
StatePublished - Sep 1 2006

Fingerprint

Estrogen Receptors
Smooth Muscle Myocytes
Smooth Muscle
Differentiation Antigens
Intercellular Signaling Peptides and Proteins
Estrogens
Cardiovascular Diseases
Lentivirus
Vascular Smooth Muscle
Caspase 3
Small Interfering RNA
Actins
Cell Differentiation
Cell Death
Phosphorylation
Ligands
Phenotype
Serum

Keywords

  • Apoptosis
  • Cardiovascular disease
  • Gene expression
  • Nuclear receptors
  • Smooth muscle differentiation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Montague, C. R., Hunter, M. G., Gavrilin, M. A., Phillips, G. S., Goldschmidt-Clermont, P., & Marsh, C. B. (2006). Activation of estrogen receptor-α reduces aortic smooth muscle differentiation. Circulation Research, 99(5), 477-484. https://doi.org/10.1161/01.RES.0000238376.72592.a2

Activation of estrogen receptor-α reduces aortic smooth muscle differentiation. / Montague, Christine R.; Hunter, Melissa G.; Gavrilin, Mikhail A.; Phillips, Gary S.; Goldschmidt-Clermont, Pascal; Marsh, Clay B.

In: Circulation Research, Vol. 99, No. 5, 01.09.2006, p. 477-484.

Research output: Contribution to journalArticle

Montague, CR, Hunter, MG, Gavrilin, MA, Phillips, GS, Goldschmidt-Clermont, P & Marsh, CB 2006, 'Activation of estrogen receptor-α reduces aortic smooth muscle differentiation', Circulation Research, vol. 99, no. 5, pp. 477-484. https://doi.org/10.1161/01.RES.0000238376.72592.a2
Montague CR, Hunter MG, Gavrilin MA, Phillips GS, Goldschmidt-Clermont P, Marsh CB. Activation of estrogen receptor-α reduces aortic smooth muscle differentiation. Circulation Research. 2006 Sep 1;99(5):477-484. https://doi.org/10.1161/01.RES.0000238376.72592.a2
Montague, Christine R. ; Hunter, Melissa G. ; Gavrilin, Mikhail A. ; Phillips, Gary S. ; Goldschmidt-Clermont, Pascal ; Marsh, Clay B. / Activation of estrogen receptor-α reduces aortic smooth muscle differentiation. In: Circulation Research. 2006 ; Vol. 99, No. 5. pp. 477-484.
@article{4aa9240b37424478a99ef9cb063a998a,
title = "Activation of estrogen receptor-α reduces aortic smooth muscle differentiation",
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-α (ERα) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ERα expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ERα and higher levels of the differentiation markers calponin and smooth muscle α-actin than SMC from women. When SMC containing low expression of ERα were transduced with a lentivirus containing ERα, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ERα expression by small interfering RNA (siRNA) in cells expressing high levels of ERα enhanced the expression of differentiation markers. ERα expression and activation reduced the phosphorylation of Smad2, a signaling molecule important in differentiation of SMC and initiated cell death through cleavage of caspase-3. We conclude that ERα activation switched SMC to a dedifferentiated phenotype and may contribute to plaque instability.",
keywords = "Apoptosis, Cardiovascular disease, Gene expression, Nuclear receptors, Smooth muscle differentiation",
author = "Montague, {Christine R.} and Hunter, {Melissa G.} and Gavrilin, {Mikhail A.} and Phillips, {Gary S.} and Pascal Goldschmidt-Clermont and Marsh, {Clay B.}",
year = "2006",
month = "9",
day = "1",
doi = "10.1161/01.RES.0000238376.72592.a2",
language = "English",
volume = "99",
pages = "477--484",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Activation of estrogen receptor-α reduces aortic smooth muscle differentiation

AU - Montague, Christine R.

AU - Hunter, Melissa G.

AU - Gavrilin, Mikhail A.

AU - Phillips, Gary S.

AU - Goldschmidt-Clermont, Pascal

AU - Marsh, Clay B.

PY - 2006/9/1

Y1 - 2006/9/1

N2 - 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-α (ERα) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ERα expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ERα and higher levels of the differentiation markers calponin and smooth muscle α-actin than SMC from women. When SMC containing low expression of ERα were transduced with a lentivirus containing ERα, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ERα expression by small interfering RNA (siRNA) in cells expressing high levels of ERα enhanced the expression of differentiation markers. ERα expression and activation reduced the phosphorylation of Smad2, a signaling molecule important in differentiation of SMC and initiated cell death through cleavage of caspase-3. We conclude that ERα activation switched SMC to a dedifferentiated phenotype and may contribute to plaque instability.

AB - 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-α (ERα) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ERα expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ERα and higher levels of the differentiation markers calponin and smooth muscle α-actin than SMC from women. When SMC containing low expression of ERα were transduced with a lentivirus containing ERα, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ERα expression by small interfering RNA (siRNA) in cells expressing high levels of ERα enhanced the expression of differentiation markers. ERα expression and activation reduced the phosphorylation of Smad2, a signaling molecule important in differentiation of SMC and initiated cell death through cleavage of caspase-3. We conclude that ERα activation switched SMC to a dedifferentiated phenotype and may contribute to plaque instability.

KW - Apoptosis

KW - Cardiovascular disease

KW - Gene expression

KW - Nuclear receptors

KW - Smooth muscle differentiation

UR - http://www.scopus.com/inward/record.url?scp=33748372947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748372947&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000238376.72592.a2

DO - 10.1161/01.RES.0000238376.72592.a2

M3 - Article

VL - 99

SP - 477

EP - 484

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 5

ER -