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Circulation. 1997 Mar 18;95(6):1505-14.

Estrogen-receptor-mediated inhibition of human endothelial cell apoptosis. Estradiol as a survival factor.

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1
Department of Medicine, St Elizabeth's Medical Center, Boston, Mass. 02135, USA.

Abstract

BACKGROUND:

A series of studies was performed to examine the ability of estradiol (E2) to protect endothelial cells from apoptosis.

METHODS AND RESULTS:

Light and transmission electron microscopy demonstrated typical features of apoptosis in human umbilical vein endothelial cells (HUVEC) exposed to tumor necrosis factor-alpha (TNF-alpha). Northern and Western blot analyses revealed induction of message and protein for the interleukin-1 beta converting enzyme (ICE), which has been shown to mediate apoptosis induced by TNF-alpha. Immunofluorescent staining of HUVEC colocalized ICE expression to apoptotic HUVEC. Direct cell counting demonstrated a significant decrease in total endothelial cell number after 24 hours of TNF-alpha exposure and a dose-dependent reversal of the effect of TNF-alpha with E2 treatment. This protective effect was abrogated by an estrogen-receptor antagonist. Fluorescence-activated cell sorting analysis revealed 39.3% apoptosis after 24 hours of TNF-alpha exposure. Treatment with E2 resulted in a 50% decrease in apoptosis. Similarly, viability assays revealed 35 +/- 4% cell death after TNF-alpha exposure. Simultaneous treatment with E2 resulted in a dose-dependent reduction of cell death to a minimum of 18 +/- 2%. The protective effect of E2 was nullified by a specific estrogen-receptor antagonist.

CONCLUSIONS:

E2 treatment resulted in a dose-dependent, receptor-mediated inhibition of TNF-alpha-induced endothelial cell apoptosis. These studies indicate that E2 may also serve a maintenance function in preventing endothelial cell death after noxious stimuli and suggest that the ICE pathway may mediate cytokine-induced apoptosis in endothelial cells. Preservation of endothelial integrity represents another mechanism that may account for the atheroprotective effect of estrogen.

PMID:
9118519
[Indexed for MEDLINE]
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