17 beta-estradiol prevents programmed cell death in cardiac myocytes

The cardioprotective effects of estrogens are clearly established. However, the underlying mechanisms are poorly understood. Because programmed cell d eath (apoptosis) probably contributes to the loss of cardiac myocytes in he art failure and because estrogens prevent apoptosis in breast cancer cells, we investigated whether the loss of cardiac myocytes by programmed cell de ath could be prevented by physiological doses of 17 beta-estradiol. Apoptos is of cultured cardiac myocytes was induced by staurosporine. 17 beta-estra diol (10 nM) had an antiapoptotic effect as determined by morphological ana lysis, vital staining using the Hoechst dye 33342 and terminal transferase dUTP nick-end labeling (TUNEL). As a potential mechanism for the antiapopto tic effect of 17 beta-estradiol we found a reduced activity of the ICE-like protease caspase-3 in hormone-treated myocytes. Furthermore, inhibition of apoptosis by estradiol was associated with a reduced activity of NF-kappa B transcription factors, particularly p65/RelA and p50, To our knowledge, t hese data provide the first, indication that 17 beta-estradiol in physiolog ical concentrations inhibits apoptosis in cardiac myocytes. The antiapoptot ic effect of estrogens might contribute to the known cardioprotective effec t of estrogens and provides a starting point for the development of future treatment options. (C) 2000 Academic Press.