Circulation. 2001;104:1419-1423
doi: 10.1161/hc3601.095577
doi: 10.1161/hc3601.095577
(Circulation. 2001;104:1419.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
17ß-Estradiol Attenuates the Development of Pressure-Overload Hypertrophy
From the Cardiovascular Research Institute Maastricht, University of Maastricht (M.v.E., J.P.M.C., B.J.J.), and the Department of Cardiology, Academisch Ziekenhuis Maastricht (H.J.J.W., P.A.D.), Maastricht, Netherlands; and the Medizinische Universitäts-Poliklinik, Bonn, Germany (C.G.).
Correspondence to Martin van Eickels, MD, Division of Cardiology, Department of Internal Medicine II, University of Bonn, Sigmund Freud Straße 25, 53105 Bonn, Germany. E-mail mvaneickels{at}lifespan.org or vaneickels@altavista.com
Background—— Cardiac hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in men and in women. Epidemiological studies indicate that estrogen replacement therapy is cardioprotective; the mechanisms involved in this process, however, are poorly understood. We therefore studied the effect of 17ß-estradiol (E2) on the development of pressure-overload hypertrophy.
Methods and Results—— Ovariectomized mice receiving E2 or placebo underwent transverse aortic constriction (TAC) or sham operation. TAC led to a significant increase in ventricular mass compared with sham operation. E2 treatment reduced cardiac hypertrophy by 31% and 26% compared with placebo 4 and 8 weeks after TAC, whereas it had no effect on the degree of pressure overload, as determined by hemodynamic measurements. Furthermore, E2 blocked the increased phosphorylation of p38-mitogen-activated protein kinase (MAPK) observed in the placebo-treated animals with TAC. No differences were observed in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 between the groups. E2 had no effect on the expression of angiotensin-converting enzyme (ACE) or the angiotensin II type 1 receptor. Ventricular atrial natriuretic peptide (ANP) expression was detected only in the animals with TAC. Compared with placebo, E2 treatment led to an increased expression of ANP in animals with pressure overload.
Conclusions—— Here, we show that E2 attenuates the hypertrophic response to pressure overload in mice. This observation demonstrates that hormone replacement therapy with E2 has direct effects on the heart and may be beneficial in the treatment of postmenopausal women to reduce cardiac hypertrophy.
Key Words: hormones • hypertrophy • myocardium • sex
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