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(Circulation. 2004;110:3270-3275.)
© 2004 American Heart Association, Inc.

Valvular Heart Disease

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; 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.

Correspondence to Vera Regitz-Zagrosek, MD, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail zagrosek{at}dhzb.de

Received May 19, 2004; revision received August 21, 2004; accepted August 25, 2004.

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

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

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

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