Estrogen receptor β protects the murine heart against left ventricular hypertrophy

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