OBJECTIVES: The main objective of the present study was to determine whether low physiological levels of estrogen directly protect cardiac cells against metabolic stress. BACKGROUND: The beneficial effect of estrogens on the cardiovascular system has been traditionally ascribed to decrease in peripheral vascular resistance and to an antiatherogenic action. Whether physiological concentrations of 17β-estradiol (E2) are also able to protect cardiomyocytes against metabolic insult directly is unknown. METHODS: Isolated ventricular cardiomyocytes were loaded with the Ca2+-sensitive fluorescent dye Fluo-3 and imaged by a digital epifluorescence imaging system. In cardiac cells preincubated with hormones and/or drugs for 8 h, metabolic stress was induced by addition and removal of 2,4-dinitrophenol (DNP). RESULTS: In cardiomyocytes, a 3-min-long exposure to chemical hypoxia, followed by reoxygenation, produced intracellular Ca2+ loading independently of gender (female: 729 ± 88 nmol/liter; male: 778 ± 97 nmol/liter). Pretreatment with E2 (10 nmol/liter) significantly reduced the magnitude of hypoxia/reoxygenation-induced Ca2+ loading in female (E2-treated: 298 ± 39 nmol/liter; untreated: 729 ± 88 nmol/liter), but not in male (E2-treated: 1029 ± 177 nmol/liter; untreated: 778 ± 97 nmol/liter) cardiac cells. The protective action of E2 was not mimicked by the inactive estrogen stereoisomer, 10 nmol/liter 17α estradiol (17α estradiol-treated: 886 ± 122 nmol/liter; untreated: 729 ± 88 nmol/liter), and was abolished by tamoxifen (1 μmol/liter), which acts as an antagonist of E2 on estrogen receptors (E2 plus tamoxifen-treated: 702 ± 98 nmol/liter; untreated: 729 ± 88 nmol/liter). CONCLUSIONS: In a gender-dependent manner, E2 directly protects cardiac cells against hypoxia-reoxygenation injury through an estrogen receptor-mediated mechanism. Such property of E2 may contribute to cardioprotection in the female gender. (C) 2000 by the American College of Cardiology.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine