17 beta-estradiol attenuates the development of pressure-overload hypertrophy

Background-Cardiac hypertrophy is an independent risk factor for cardiovasc ular morbidity and mortality in men and in women. Epidemiological studies i ndicate that estrogen replacement therapy is cardioprotective; the mechanis ms involved in this process, however, are poorly understood. We therefore s tudied the effect of 17 beta -estradiol (E-2) on the development of pressur e-overload hypertrophy. Methods and Results-Ovariectomized mice receiving E-2 or placebo underwent transverse aortic constriction (TAC) or sham operation. TAC led to a signif icant increase in ventricular mass compared with sham operation. E-2 treatm ent 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 overl oad, as determined by hemodynamic measurements. Furthermore, E-2 blocked th e increased phosphorylation of p38-mitogen-activated protein kinase (MAPK) observed in the placebo-treated animals with TAC. No differences were obser ved in the phosphorylation of extracellular signal-regulated kinase (ERK) 1 /2 and c-Jun N-terminal kinase (JNK) 1/2 between the groups. E-2 had no eff ect on the expression of angiotensin-converting enzyme (ACE) or the angiote nsin I type 1 receptor. Ventricular atrial natriuretic peptide (ANP) expres sion was detected only in the animals with TAC. Compared with placebo, E-2 treatment led to an increased expression of ANP in animals with pressure ov erload. Conclusions-Here, we show that E-2 attenuates the hypertrophic response to pressure overload in mice. This observation demonstrates that hormone repla cement therapy with E-2 has direct effects on the heart and may be benefici al in the treatment of postmenopausal women to reduce cardiac hypertrophy.