title: Estrogen receptor alpha up-regulation and redistribution in human heart failure.
abstract: 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 (ERalpha) expression, localization, and association with structural proteins was altered in end stage-failing hearts. We found a 1.8-fold increase in ERalpha mRNA and protein in end-stage human dilated cardiomyopathy (DCM, n=41), as compared with controls (n=25). ERalpha was visualized by confocal immunofluorescence microscopy and localized to the cytoplasm, sarcolemma, intercalated discs and nuclei of cardiomyocytes. Immunofluorescence studies demonstrated colocalization of ERalpha with beta-catenin at the intercalated disc in control hearts and immunoprecipitation studies confirmed complex formation of both proteins. Interestingly, the ERalpha/beta-catenin colocalization was lost at the intercalated disc in DCM hearts. Thus, the ERalpha/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 ERalpha expression may represent a compensatory process to contribute to the stability of cardiac intercalated discs.
authors: Center for Cardiovascular Research, Charite and Deutsches Herzzentrum Berlin, Germany.
authors: Shokoufeh
authors: S
authors: Mahmoodzadeh
authors: Sarah
authors: S
authors: Eder
authors: Johannes
authors: J
authors: Nordmeyer
authors: Elisabeth
authors: E
authors: Ehler
authors: Otmar
authors: O
authors: Huber
authors: Peter
authors: P
authors: Martus
authors: Jörg
authors: J
authors: Weiske
authors: Reinhard
authors: R
authors: Pregla
authors: Roland
authors: R
authors: Hetzer
authors: Vera
authors: V
authors: Regitz-Zagrosek