Published online before print April 20, 2006, doi: 10.1161/01.ATV.0000223344.11128.23
© 2006 American Heart Association, Inc.
Vascular Biology |
Estrogen Receptor ß Protects the Murine Heart Against Left Ventricular Hypertrophy
From the Department of Cardiology (F.A.B., D.L., E.D.), Cardiovascular Research Institute Maastricht, University Hospital Maastricht, the Netherlands; Physiologisches Institut II (R.M.), Bonn Germany; Department of Pharmacology (P.Z.), Organon NV, the Netherlands; Department of Pharmacology (B.J.), Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands; Department of Molecular Genetics (G.v.E.), Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands; Medizinische Universitätspoliklinik (C.G.), Bonn, Germany; Interuniversity Cardiology Institute of the Netherlands (P.A.D.) and Department of Cardiology (P.A.D.), Heart Lung Center Utrecht, the Netherlands.
Correspondence to Dr C. Grohé, Medizinische Universitäts-Poliklinik, Wilhelmstr. 35-37, Universitätsklinikum Bonn, 53111 Bonn, Germany. E-mail c.grohe{at}uni-bonn.de
Background— Left ventricular hypertrophy (LVH) displays significant gender-based differences. 17ß-estradiol (E2) plays an important role in this process because it can attenuate pressure overload hypertrophy via 2 distinct estrogen receptors (ERs): ER
and ERß. However, which ER is critically involved in the modulation of LVH is poorly understood. We therefore used ER-deficient (ER–/–) and ERß-deficient (ERß–/–) mice to analyze the respective ER-mediated effects.
Methods and Results— Respective ER-deficient female mice were ovariectomized and were given E2 or placebo subcutaneously using 60-day release pellets. After 2 weeks, they underwent transverse aortic constriction (TAC) or sham operation. In ER–/– animals, TAC led to a significant increase in ventricular mass compared with sham operation. E2 treatment reduced TAC induced cardiac hypertrophy significantly in wild-type (WT) and ER–/– mice but not in ERß–/– mice. Biochemical analysis showed that E2 blocked the increased phosphorylation of p38–mitogen-activated protein kinase observed in TAC-treated ER–/– mice. Moreover, E2 led to an increase of ventricular atrial natriuretic factor expression in WT and ER–/– mice.
Conclusions— These findings demonstrate that E2, through ERß-mediated mechanisms, protects the murine heart against LVH.
E2 protects the murine heart against LVH via ERß. Presence of E2 antagonizes the increase in heart weight with TAC. This protective effect is played by blocking the increased phosphorylation of p38-MAPK and increasing the expression of ANF. ER appears to be involved in regulation of other processes.
Key Words: hypertrophy • hormones • myocardium • gender
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