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Upregulation of myocardial estrogen receptors in human aortic stenosis.

Authors: Nordmeyer, J  Eder, S  Mahmoodzadeh, S  Martus, P  Fielitz, J  Bass, J  Bethke, N  Zurbrugg, HR  Pregla, R  Hetzer, R  Regitz-Zagrosek, V 
Citation: Nordmeyer J, etal., Circulation. 2004 Nov 16;110(20):3270-5. Epub 2004 Nov 8.
Pubmed: (View Article at PubMed) PMID:15533858
DOI: Full-text: DOI:10.1161/01.CIR.0000147610.41984.E8

BACKGROUND: Estrogen receptor (ER)-mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but ER expression in the human heart and its relation to hypertrophy-mediated gene expression have not yet been analyzed. We therefore investigated sex- and disease-dependent alterations of myocardial ER expression in human aortic stenosis together with the expression of hypertrophy-related genes. METHODS AND RESULTS: ER-alpha and -beta, calcineurin A-beta, and brain natriuretic peptide (BNP) mRNA were quantified by real-time polymerase chain reaction in left ventricular biopsies from patients with aortic valve stenosis (n=14) and control hearts with normal systolic function (n=17). ER protein was quantified by immunoblotting and visualized by immunofluorescence confocal microscopy. ER-alpha mRNA and protein were increased 2.6-fold (P=0.003) and 1.7-fold (P=0.026), respectively, in patients with aortic valve stenosis. Left ventricular ER-beta mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-alpha and -beta were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-beta and calcineurin A-beta mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER-alpha or -beta and BNP mRNA. CONCLUSIONS: ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.

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RGD Object Information
RGD ID: 1580704
Created: 2006-08-21
Species: All species
Last Modified: 2006-08-21
Status: ACTIVE



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