Document Detail

Activation of estrogen receptor-alpha reduces aortic smooth muscle differentiation.
MedLine Citation:
PMID:  16873715     Owner:  NLM     Status:  MEDLINE    
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.
Christine R Montague; Melissa G Hunter; Mikhail A Gavrilin; Gary S Phillips; Pascal J Goldschmidt-Clermont; Clay B Marsh
Related Documents :
14614325 - Specific inhibition of dnmt1 by antisense oligonucleotides induces re-expression of est...
15709005 - Positive and negative regulation of chicken anemia virus transcription.
18448105 - Steroid receptor expression in the developing copulatory system of the green anole liza...
16460835 - Tissue-specific expression of clec2g in mice.
3821725 - Transient response of amplified metallothionein genes in cho cells to induction by alph...
22653845 - Activation of wnt signalling promotes development of dysplasia in barrett's oesophagus.
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:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  477-84     Citation Subset:  IM    
Department of Medicine, Ohio State University College of Medicine, Columbus 43210, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Aorta / cytology*,  metabolism
Cell Differentiation / drug effects,  physiology*
Cells, Cultured
Estrogen Receptor alpha / genetics,  metabolism,  physiology*
Middle Aged
Muscle, Smooth, Vascular / cytology*,  metabolism
Myocytes, Smooth Muscle / cytology*,  metabolism
RNA, Small Interfering / pharmacology
Smad2 Protein / antagonists & inhibitors,  metabolism
Transduction, Genetic
Transforming Growth Factor beta / pharmacology
Transforming Growth Factor beta1
Grant Support
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 HL063800-05/HL/NHLBI NIH HHS; R01 HL066108-04/HL/NHLBI NIH HHS; R01 HL067176-04/HL/NHLBI NIH HHS
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
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

Previous Document:  Impaired endothelium-derived hyperpolarizing factor-mediated dilations and increased blood pressure ...
Next Document:  Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on...