Document Detail

Estrogen-induced SDF-1 production is mediated by estrogen receptor-α in female hearts after acute ischemia and reperfusion.
MedLine Citation:
PMID:  21719062     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Gender differences exist in myocardial response to acute ischemia/reperfusion (I/R) injury and estrogen mediates cardioprotection in the female heart after I/R. Accumulating evidence has indicated that stromal cell-derived factor-1 (SDF-1) is increased in the ischemic heart and initiates cardioprotective effects. However, it is unknown whether SDF-1 plays a role in gender-specific response to myocardial I/R and in estrogen-induced acute protection. Therefore, we hypothesize that (1) increased SDF-1 production will be observed in female hearts compared with male hearts in response to I/R, which is attributable to the effect of estrogen; and that (2) estrogen receptor (ER)α, not ERβ mediates estrogen-contributed SDF-1 expression in female hearts after I/R.
METHODS: Heart tissue subjected to I/R injury was assessed for myocardial expression of SDF-1 (by enzyme-linked immunosorbent assay) and SDF-1 receptor-CXCR4 (Western blot). Groups were as follows: Rat hearts from adult male, female, ovariectomized female (OVX F), and male and OVX F supplemented with chronic 17β-estradiol (E2), and mouse hearts from adult male and female wild-type, ERα knockout (ERαKO) and ERβKO.
RESULTS: I/R significantly increased myocardial SDF-1 expression in both genders. Higher levels of SDF-1 existed in female hearts after I/R compared with males. Depletion of endogenous estrogen by ovariectomy reduced cardiac SDF-1 production in females after I/R. E2 supplementation significantly restored SDF-1 expression in OVX F and males compared with their counterparts. Notably, ablation of ERα, not ERβ, markedly decreased SDF-1 production in females after I/R. Unlike SDF-1, cardiac CXCR4 expression was not affected by gender, sex hormone, or ERs in the ischemic heart.
CONCLUSION: Our study represents the first evidence that female hearts exhibit higher levels of SDF-1 expression compared with males after acute I/R. This increased myocardial SDF-1 production in females is partly owing to effect of estrogen through ERα, but not ERβ.
Chunyan Huang; Hongmei Gu; Yu Wang; Meijing Wang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-30
Journal Detail:
Title:  Surgery     Volume:  150     ISSN:  1532-7361     ISO Abbreviation:  Surgery     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-01     Completed Date:  2011-09-20     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  197-203     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 Mosby, Inc. All rights reserved.
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MeSH Terms
Chemokine CXCL12 / metabolism*
Estrogen Receptor alpha / metabolism*
Estrogens / metabolism*
Mice, Inbred C57BL
Mice, Knockout
Myocardial Reperfusion Injury / metabolism*
Sex Factors
Grant Support
Reg. No./Substance:
0/Chemokine CXCL12; 0/Estrogen Receptor alpha; 0/Estrogens

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