(Circulation. 1996;94:1402-1407.)
© 1996 American Heart Association, Inc.
Articles |
the Department of Pediatrics, Northwestern University Medical School, Chicago, Ill (S.K.-S., S.C.H., H.W.S.); the Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Md (K.A.M., H.K.K.); the Department of Internal Medicine, Fundacio Clinic, Barcelona, Spain (M.C.C.); the Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC (M.B.M.); and the Ben May Institute, University of Chicago (Ill) (G.L.G.).
Correspondence to Seunghee Kim-Schulze, PhD, Pediatrics W-140, 303 E Chicago Ave, Chicago, IL 60611-3008. E-mail ski057@nwu.edu.
Background Premenopausal women have much lower susceptibility to coronary artery disease than do men or postmenopausal women. It has been proposed that estrogen plays a role in cardioprotection, but little information is available regarding the mechanism by which estrogen may help to protect the vasculature. Here, we describe an estrogen receptor (ER) in human coronary artery and umbilical vein endothelial cells.
Methods and Results Human umbilical vein endothelial cells and human coronary artery endothelial cells were cultured in hormone-free medium for 48 hours before experiments. Estradiol (3.7 nmol/L) added to cultures promoted proliferation by a mechanism that is inhibited by the specific ER antagonist ICI182,780. Estradiol-treated cells incorporated twice the [3H]thymidine of hormone-free cells; this increase was prevented by ICI182,780. Endothelial cells from both sources stained in a nuclear pattern with an ER-specific antibody. Ribonuclease protection assay detected mRNA for the ER. Ligand-binding studies estimated 2x104 to 8x104 receptors per cell and a Kd of
5 nmol/L. Interaction of ERs with a consensus estrogen response element was shown by an electrophoretic mobility shift assay. In addition, an antibody against the ER supershifted the protein-DNA complex.
Conclusions These studies define the presence of an ER in human coronary artery and umbilical vein endothelial cells. They support the hypothesis that cardioprotective effects of estrogen are mediated, at least in part, through a classic steroid hormone receptor mechanism.
Key Words: estrogen endothelium receptors cells
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