Estrogen receptor β protects the murine heart against left ventricular hypertrophy

Abstract

BACKGROUND - Left ventricular hypertrophy (LVH) displays significant gender-based differences. 17β-estradiol (E2) plays an important role in this process because it can attenuate pressure overload hypertrophy via 2 distinct estrogen receptors (ERs): ERα and ERβ. However, which ER is critically involved in the modulation of LVH is poorly understood. We therefore used ERα-deficient (ERα/) and ERβ-deficient (ERβ/) 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 ERα/ 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 ERα/ mice but not in ERβ mice. Biochemical analysis showed that E2 blocked the increased phosphorylation of p38-mitogen-activated protein kinase observed in TAC-treated ERα/ mice. Moreover, E2 led to an increase of ventricular atrial natriuretic factor expression in WT and ERα/ mice. CONCLUSIONS - These findings demonstrate that E2, through ERβ-mediated mechanisms, protects the murine heart against LVH. © 2006 American Heart Association, Inc.