Document Detail


Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.
MedLine Citation:
PMID:  23645678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.
Authors:
Alexander R Mackie; Prasanna Krishnamurthy; Suresh K Verma; Tina Thorne; Veronica Ramirez; Gangjian Qin; Tatiana Abramova; Hiromichi Hamada; Douglas W Losordo; Raj Kishore
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-05-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-24     Completed Date:  2013-09-06     Revised Date:  2014-06-24    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18022-34     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Blotting, Western
Cell Movement / drug effects*
Cell Survival / drug effects
Cells, Cultured
Endothelial Cells / drug effects*,  metabolism,  physiology
Estradiol / metabolism,  pharmacology*
Estrogens / metabolism,  pharmacology
Ethanol / pharmacology*
Female
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Myocardial Infarction / genetics,  metabolism,  physiopathology
Myocardium / metabolism*,  pathology
Nitric Oxide Synthase Type III / deficiency,  genetics
Ovariectomy
Protein Binding / drug effects
Receptors, Estrogen / metabolism
Stem Cells / drug effects*,  metabolism,  physiology
Grant Support
ID/Acronym/Agency:
HL053354/HL/NHLBI NIH HHS; HL091983/HL/NHLBI NIH HHS; HL093439/HL/NHLBI NIH HHS; HL095874/HL/NHLBI NIH HHS; HL105597/HL/NHLBI NIH HHS; HL108795/HL/NHLBI NIH HHS; HL113541/HL/NHLBI NIH HHS; R01 HL105597/HL/NHLBI NIH HHS; R01 HL113541/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 0/Receptors, Estrogen; 3K9958V90M/Ethanol; 4TI98Z838E/Estradiol; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse
Comments/Corrections

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