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

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.