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

Article

关键词: ATRIAL-NATRIURETIC-PEPTIDE;    LEFT-VENTRICULAR HYPERTROPHY;    IN-VITRO;    ESTROGEN;    EXPRESSION;    PROGESTERONE;    PATHWAYS;    MYOCYTES;    STRESS;   

DOI  :  10.1161/hc3601.095577

来源: SCIE

【 摘 要 】

Background-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 17 beta -estradiol (E-2) on the development of pressure-overload hypertrophy. Methods and Results-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 I 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. Conclusions-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.

【 授权许可】

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