Document Detail


Activation of estrogen receptor-alpha reduces aortic smooth muscle differentiation.
MedLine Citation:
PMID:  16873715     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-alpha (ERalpha) by agonists or by growth factors altered SMC function. To determine the effect of growth factors, estrogen, and ERalpha expression on SMC differentiation, human aortic SMC were cultured in serum-free conditions for 10 days. SMC from men had lower spontaneous expression of ERalpha and higher levels of the differentiation markers calponin and smooth muscle alpha-actin than SMC from women. When SMC containing low expression of ERalpha were transduced with a lentivirus containing ERalpha, activation of the receptor by ligands or growth factors reduced differentiation markers. Conversely, inhibiting ERalpha expression by small interfering RNA (siRNA) in cells expressing high levels of ERalpha enhanced the expression of differentiation markers. ERalpha 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 ERalpha activation switched SMC to a dedifferentiated phenotype and may contribute to plaque instability.
Authors:
Christine R Montague; Melissa G Hunter; Mikhail A Gavrilin; Gary S Phillips; Pascal J Goldschmidt-Clermont; Clay B Marsh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-07-27
Journal Detail:
Title:  Circulation research     Volume:  99     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-01     Completed Date:  2006-10-02     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  477-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aorta / cytology*,  metabolism
Cell Differentiation / drug effects,  physiology*
Cells, Cultured
Estrogen Receptor alpha / genetics,  metabolism,  physiology*
Female
Humans
Ligands
Male
Middle Aged
Muscle, Smooth, Vascular / cytology*,  metabolism
Myocytes, Smooth Muscle / cytology*,  metabolism
Phosphorylation
RNA, Small Interfering / pharmacology
Smad2 Protein / antagonists & inhibitors,  metabolism
Transduction, Genetic
Transforming Growth Factor beta / pharmacology
Transforming Growth Factor beta1
Grant Support
ID/Acronym/Agency:
5F32 HL09550/HL/NHLBI NIH HHS; HL066108-04/HL/NHLBI NIH HHS; HL63800-05/HL/NHLBI NIH HHS; HL67176-04/HL/NHLBI NIH HHS; HL70294-03/HL/NHLBI NIH HHS; R01 HL063800/HL/NHLBI NIH HHS; R01 HL066108/HL/NHLBI NIH HHS; R01 HL067176/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Ligands; 0/RNA, Small Interfering; 0/Smad2 Protein; 0/TGFB1 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1
Comments/Corrections
Comment In:
Circ Res. 2006 Sep 1;99(5):459-61   [PMID:  16946140 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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