Published Online
on November 8, 2004

A more recent version of this article appeared on November 16, 2004

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Submitted on May 19, 2004
Revised on August 21, 2004
Accepted on August 25, 2004

Upregulation of Myocardial Estrogen Receptors in Human Aortic Stenosis

Johannes Nordmeyer AS, Sarah Eder AS, Shokoufeh Mahmoodzadeh PhD, Peter Martus PhD, Jens Fielitz MD, Jan Bass AS, Nicole Bethke AS, Heinz R. Zurbrügg MD, Reinhard Pregla MD, Roland Hetzer MD, and Vera Regitz-Zagrosek MD^*

From Cardiovascular Disease in Women, Charite and Deutsches Herzzentrum Berlin (J.N., S.E., S.M., J.F., J.B., N.B., V.R.-Z); Charite and Deutsches Herzzentrum Berlin (R.H.); Klinik für Herz-, Gefäss- und Thoraxchirurgie, Deutsches Herzzentrum Berlin (H.R.Z., R.P.); and Institute for Medical Informatics, Biometry and Epidemiology, Charite (P.M.), Berlin, Germany.

^* To whom correspondence should be addressed. E-mail: zagrosek{at}dhzb.de.

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- and -, calcineurin A-, 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- 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- mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER- and - were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER- and calcineurin A- mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER- or - and BNP mRNA.

Conclusions--ER- and - in the human heart are upregulated by myocardial pressure load.

Key words: receptors, estrogen • stenosis, aortic valve • hypertrophy

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