This Article Full Text Full Text (PDF) All Versions of this Article: 91/12/4995    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seli, E. Articles by Arici, A. Search for Related Content PubMed PubMed Citation Articles by Seli, E. Articles by Arici, A. Related Collections Cardiovascular Endocrinology Female Endocrinology

Estradiol Increases Apoptosis in Human Coronary Artery Endothelial Cells by Up-Regulating Fas and Fas Ligand Expression

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063

Address all correspondence and requests for reprints to: Aydin Arici, M.D., Section of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063. E-mail: aydin.arici{at}yale.edu.

Context: In animal models, estrogen inhibits atherogenesis by inhibiting many of the early steps of atherosclerotic plaque formation. However, the lack of cardioprotective effect by postmenopausal hormone replacement therapy and possible increase in cardiovascular events observed during the first year after the initiation of hormone replacement therapy may suggest that once the plaque is formed, estrogen may have additional effects that may counteract its beneficial outcomes. Indeed, the effect of estrogen on plaque stability has not been identified.

Objective: We hypothesized that 17ß-estradiol (E₂) may cause increased apoptosis in human coronary artery endothelial cells (HCAECs). This effect would explain an adverse effect on plaque stability in vivo.

Intervention(s) and Main Outcome Measure(s): The effect of E₂ on apoptosis, cell proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL) in cultured HCAECs was evaluated.

Results: HCAECs in culture treated with E₂ showed an increase in DNA strand breaks and nuclear fragmentation indicative of apoptosis. E₂ treatment also induced a significant concentration-dependent increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to E₂ treatments.

Conclusions: E₂ increases the apoptosis in cultured HCAECs. Enhanced Fas and FasL expressions in response to E₂ suggest that activation of the Fas/FasL pathway may be a mediator of the proapoptotic effects of E₂ in these cells.

This article has been cited by other articles:

				W. Murk, C. S. Atabekoglu, H. Cakmak, A. Heper, A. Ensari, U. A. Kayisli, and A. Arici Extracellularly Signal-Regulated Kinase Activity in the Human Endometrium: Possible Roles in the Pathogenesis of Endometriosis J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3532 - 3540. [Abstract] [Full Text] [PDF]

				P. P. Liu and M. Fukuoka Sex Hormones as Novel Risk Biomarkers for Atherosclerosis in Peripheral Vascular Disease J. Am. Coll. Cardiol., September 11, 2007; 50(11): 1077 - 1079. [Full Text] [PDF]