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

Abstract

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 17beta-estradiol (E(2)) on the development of pressure-overload hypertrophy. Ovariectomized mice receiving E(2) or placebo underwent transverse aortic constriction (TAC) or sham operation. TAC led to a significant increase in ventricular mass compared with sham operation. E(2) 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, E(2) 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. E(2) 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, E(2) treatment led to an increased expression of ANP in animals with pressure overload. Here, we show that E(2) attenuates the hypertrophic response to pressure overload in mice. This observation demonstrates that hormone replacement therapy with E(2) has direct effects on the heart and may be beneficial in the treatment of postmenopausal women to reduce cardiac hypertrophy.