Copyright © 2005, European Society of Cardiology
Estrogen improves cardiac recovery after ischemia/reperfusion by decreasing tumor necrosis factor-
232 HMRC Departments of Obstetrics/Gynecology and Physiology, Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
* Corresponding author. Tel.: +1 780 492 1864; fax: +1 780 492 1308. Email address: sandra.davidge{at}ualberta.ca
Background: Estrogen has cardioprotective effects on ischemia/reperfusion (I/R). Tumor necrosis factor alpha (TNF
) is an inflammatory cytokine with depressor effects on myocardial function and has been suggested to mediate I/R injury. Whether cardiac TNFlevels are influenced by estrogen status is unknown. We investigated the effect of estrogen on TNFlevels and TNFreceptors in the ischemic heart and its role in estrogen modulation of I/R injury.
Methods: Hearts were isolated from ovariectomized Sprague-Dawley female rats that were treated with either estrogen or placebo for 4 weeks. Working heart preparations were subjected to global, no-flow ischemia (25 min) followed by reperfusion (40 min).
Results: I/R increased TNFlevels in coronary effluent and in the left ventricle (LV) of estrogen-deficient rats, which were decreased by estrogen replacement. Moreover, estrogen improved functional recovery (55.0 ± 5.0% vs. 22.0 ± 7.0%, P<0.05), decreased LV apoptosis, and reduced myocardial necrosis. To further evaluate the role of TNFin I/R injury, a selective TNFinhibitor (etanercept) was used in vitro before the ischemic insult. TNFinhibition improved functional recovery (39 ± 4.4% vs. 22.0 ± 7.0%, P<0.05) and reduced apoptosis and myocardial necrosis in estrogen-deficient animals but did not have a summative protective effect in the hearts of estrogen-replaced animals.
Conclusions: These data indicate that estrogen modulates cardiac expression of TNFand TNFreceptors. Moreover, the cardioprotective effects of estrogen are in part mediated by regulation of TNFlevels in the ischemic heart.
KEYWORDS Cytokines; Inflammation; Ischemia; Reperfusion; Hormones
1 Both authors have contributed equally to this work.
Time for primary review 47 days
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