Estrogen receptor alpha up-regulation and redistribution in human heart failure

被引:113
作者
Mahmoodzadeh, Shokoufeh
Eder, Sarah
Nordmeyer, Johannes
Ehler, Elisabeth
Huber, Otmar
Martus, Peter
Weiske, Joerg
Pregla, Reinhard
Hetzer, Roland
Regitz-Zagrosek, Vera
机构
[1] Deutsch Herzzentrum Berlin, D-13353 Berlin, Germany
[2] Charite, Cardiovasc Res Ctr, Berlin, Germany
[3] DHZB, Klin Herz Gefass & Thoraxchirurg, Berlin, Germany
[4] DHZB Berlin, Klin Herz Gefass & Thoraxchirurg, Berlin, Germany
[5] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England
[6] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England
[7] Inst Clin Chem & Pathobiochem, Berlin, Germany
[8] Inst Med Stat & Clin Epidemiol, Berlin, Germany
关键词
estrogen receptors; dilated cardiomyopathy; intercalated disc;
D O I
10.1096/fj.05-5148com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Clinical and animal studies suggest that estrogen receptors are involved in the development of myocardial hypertrophy and heart failure. In this study, we investigated whether human myocardial estrogen receptor alpha (ER alpha) expression, localization, and association with structural proteins was altered in end stage-failing hearts. We found a 1.8-fold increase in ER alpha mRNA and protein in end-stage human dilated cardiomyopathy ( DCM, n = 41), as compared with controls (n = 25). ER alpha was visualized by confocal immunofluorescence microscopy and localized to the cytoplasm, sarcolemma, intercalated discs and nuclei of cardiomyocytes. Immunofluorescence studies demonstrated colocalization of ER alpha with beta-catenin at the intercalated disc in control hearts and immunoprecipitation studies confirmed complex formation of both proteins. Interestingly, the ER alpha/beta-catenin colocalization was lost at the intercalated disc in DCM hearts. Thus, the ER alpha/beta-catenin colocalization in the intercalated disc may be of functional relevance and a loss of this association may play a role in the progression of heart failure. The increase of total ER alpha expression may represent a compensatory process to contribute to the stability of cardiac intercalated discs.
引用
收藏
页码:926 / 934
页数:9
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