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Circulation, Vol 89, 1501-1510, Copyright © 1994 by American Heart Association
DW Losordo, M Kearney, EA Kim, J Jekanowski and JM Isner
BACKGROUND: The relative absence of coronary atherosclerosis in
premenopausal women has been established. Estrogen is presumed to play a
role in the protection of coronary arteries from atherosclerosis, and part
of this protective effect appears to be mediated by amelioration of serum
lipid profiles. However, all of the atheroprotective effect of estrogen is
not explained by alteration of serum lipids. In this study, we attempt to
identify evidence of estrogen receptors in coronary artery specimens of
female patients and in human vascular smooth muscle cells. METHODS AND
RESULTS: Postmortem coronary artery specimens were obtained from
premenopausal (n = 18) and postmenopausal (n = 22) women who died with
significant coronary artery disease (n = 19) and from noncardiac causes
with normal coronary arteries (n = 21). Sections were examined for evidence
of estrogen receptor expression using a monoclonal antibody stain.
Radioligand binding assays for estrogen receptors were performed on human
vascular smooth muscle cells in culture, and gel retardation assays were
performed to confirm the presence of functional estrogen receptors.
Estrogen receptor expression was identified by immunostaining in a total of
21 coronary arteries, with the majority of normal arteries (15 positive of
21 total, P = .0117) demonstrating evidence of estrogen receptor
expression. Conversely, a minority (6 of 19, P = NS) of atherosclerotic
arteries were positive for estrogen receptor expression. Furthermore, the
relation between estrogen receptor expression and absence of coronary
atherosclerosis was most evident in premenopausal subjects, with 10 of 12
normal arteries in this group demonstrating evidence of estrogen receptors,
whereas only 1 of 6 atherosclerotic coronary arteries was positive (P =
.0062). Radioligand binding assays confirmed the presence of estrogen
receptors at significant concentrations in intact human vascular smooth
muscle cells. Gel retardation assays also documented the presence of
functional estrogen receptors in extracts from human vascular smooth muscle
cells. CONCLUSIONS: This investigation provides evidence of estrogen
receptors in smooth muscle cells from human coronary arteries. The
demonstrated relation between the presence of the receptors and the absence
of atherosclerosis in premenopausal women suggests that these receptors may
play a functional role in coronary atheroprotection.
ARTICLES
Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women
Department of Medicine (Cardiology), St Elizabeth's Hospital, Tufts University School of Medicine, Boston, Mass. 02135.
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H. Lou, M. B. Martin, A. Stoica, P. W. Ramwell, and M. L. Foegh Upregulation of Estrogen Receptor-{alpha} Expression in Rabbit Cardiac Allograft Circ. Res., November 2, 1998; 83(9): 947 - 951. [Abstract] [Full Text] [PDF]
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 R. D. Minshall, K. Miyagawa, C. C. Chadwick, M. J. Novy, and K. Hermsmeyer In vitro modulation of primate coronary vascular muscle cell reactivity by ovarian steroid hormones FASEB J, October 1, 1998; 12(13): 1419 - 1429. [Abstract] [Full Text]
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 O C E Gebara, M A Mittleman, B W Walsh, I Lipinska, F K Welty, G Bellotti, J E Muller, F K Sacks, and G H Tofler Fibrinolytic potential is significantly increased by oestrogen treatment in postmenopausal women with mild dyslipidaemia Heart, September 1, 1998; 80(3): 235 - 239. [Abstract] [Full Text]
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S. Kim-Schulze, W. L. Lowe Jr, and H. W. Schnaper Estrogen Stimulates Delayed Mitogen-Activated Protein Kinase Activity in Human Endothelial Cells via an Autocrine Loop That Involves Basic Fibroblast Growth Factor Circulation, August 4, 1998; 98(5): 413 - 421. [Abstract] [Full Text] [PDF]
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V. Lindner, S. K. Kim, R. H. Karas, G. G. J. M. Kuiper, J.-A. Gustafsson, and M. E. Mendelsohn Increased Expression of Estrogen Receptor-ß mRNA in Male Blood Vessels After Vascular Injury Circ. Res., July 27, 1998; 83(2): 224 - 229. [Abstract] [Full Text] [PDF]
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 I. Hernandez, J. L. Delgado, L. F. Carbonell, M. C. Perez, and T. Quesada Hemodynamic effect of 17beta -estradiol in absence of NO in ovariectomized rats: role of angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, April 1, 1998; 274(4): R970 - R978. [Abstract] [Full Text] [PDF]
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 J. R. Sowers Diabetes Mellitus and Cardiovascular Disease in Women Arch Intern Med, March 23, 1998; 158(6): 617 - 621. [Abstract] [Full Text] [PDF]
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 C. H. Selzman, T. A. Whitehill, B. D. Shames, E. J. Pulido, B. C. Cain, and A. H. Harken The Biology of Estrogen-Mediated Repair of Cardiovascular Injury Ann. Thorac. Surg., March 1, 1998; 65(3): 868 - 874. [Abstract] [Full Text] [PDF]
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D. F. Skafar, R. Xu, J. Morales, J. Ram, and J. R. Sowers Female Sex Hormones and Cardiovascular Disease in Women J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3913 - 3918. [Abstract] [Full Text] [PDF]
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K. Sudhir, E. Ko, C. Zellner, H. E. Wong, S. J. Hutchison, T. M. Chou, and K. Chatterjee Physiological Concentrations of Estradiol Attenuate Endothelin 1–Induced Coronary Vasoconstriction In Vivo Circulation, November 18, 1997; 96(10): 3626 - 3632. [Abstract] [Full Text]
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K. Sudhir, T. M. Chou, K. Chatterjee, E. P. Smith, T. C. Williams, J. P. Kane, M. J. Malloy, K. S. Korach, and G. M. Rubanyi Premature Coronary Artery Disease Associated With a Disruptive Mutation in the Estrogen Receptor Gene in a Man Circulation, November 18, 1997; 96(10): 3774 - 3777. [Abstract] [Full Text]
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 V. L. Baker, V. A. Chao, J. T. Murai, C. J. Zaloudek, and R. N. Taylor Human Umbilical Vessels and Cultured Umbilical Vein Endothelial and Smooth Muscle Cells Lack Detectable Protein and mRNA Endocing Estrogen Receptors Reproductive Sciences, November 1, 1997; 4(6): 316 - 324. [Abstract] [PDF]
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S. Bonthu, D. D. Heistad, D. A. Chappell, K. G. Lamping, and F. M. Faraci Atherosclerosis, Vascular Remodeling, and Impairment of Endothelium-Dependent Relaxation in Genetically Altered Hyperlipidemic Mice Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2333 - 2340. [Abstract] [Full Text]
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Y. Matsubara, M. Murata, K. Kawano, T. Zama, N. Aoki, H. Yoshino, G. Watanabe, K. Ishikawa, and Y. Ikeda Genotype Distribution of Estrogen Receptor Polymorphisms in Men and Postmenopausal Women From Healthy and Coronary Populations and Its Relation to Serum Lipid Levels Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3006 - 3012. [Abstract] [Full Text]
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B. Bruck, U. Brehme, N. Gugel, S. Hanke, G. Finking, C. Lutz, N. Benda, F. W. Schmahl, R. Haasis, and H. Hanke Gender-Specific Differences in the Effects of Testosterone and Estrogen on the Development of Atherosclerosis in Rabbits Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2192 - 2199. [Abstract] [Full Text]
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J. K. Williams, E. K. Honore, and M. R. Adams Contrasting Effects of Conjugated Estrogens and Tamoxifen on Dilator Responses of Atherosclerotic Epicardial Coronary Arteries in Nonhuman Primates Circulation, September 16, 1997; 96(6): 1970 - 1975. [Abstract] [Full Text]
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 A. K. Morey, A. Pedram, M. Razandi, B. A. Prins, R.-M. Hu, E. Biesiada, and E. R. Levin Estrogen and Progesterone Inhibit Vascular Smooth Muscle Proliferation Endocrinology, August 1, 1997; 138(8): 3330 - 3339. [Abstract] [Full Text] [PDF]
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K. Krasinski, I. Spyridopoulos, T. Asahara, R. van der Zee, J. M. Isner, and D. W. Losordo Estradiol Accelerates Functional Endothelial Recovery After Arterial Injury Circulation, April 1, 1997; 95(7): 1768 - 1772. [Abstract] [Full Text]
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I. Spyridopoulos, A. B. Sullivan, M. Kearney, J. M. Isner, and D. W. Losordo Estrogen-Receptor–Mediated Inhibition of Human Endothelial Cell Apoptosis : Estradiol as a Survival Factor Circulation, March 18, 1997; 95(6): 1505 - 1514. [Abstract] [Full Text]
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B. Imthurn, M. Rosselli, A. W. Jaeger, P. J. Keller, and R. K. Dubey Differential Effects of Hormone-Replacement Therapy on Endogenous Nitric Oxide (Nitrite/Nitrate) Levels in Postmenopausal Women Substituted with 17{beta}-Estradiol Valerate and Cyproterone Acetate or Medroxyprogesterone Acetate J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 388 - 394. [Abstract] [Full Text] [PDF]
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S. Kim-Schulze, K. A. McGowan, S. C. Hubchak, M. C. Cid, M. B. Martin, H. K. Kleinman, G. L. Greene, and H. W. Schnaper Expression of an Estrogen Receptor by Human Coronary Artery and Umbilical Vein Endothelial Cells Circulation, September 15, 1996; 94(6): 1402 - 1407. [Abstract] [Full Text]
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C. D. Venkov, A. B. Rankin, and D. E. Vaughan Identification of Authentic Estrogen Receptor in Cultured Endothelial Cells: A Potential Mechanism for Steroid Hormone Regulation of Endothelial Function Circulation, August 15, 1996; 94(4): 727 - 733. [Abstract] [Full Text]
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H. Hanke, S. Hanke, G. Finking, A. Muhic-Lohrer, A. O. Muck, F. W. Schmahl, R. Haasis, and V. Hombach Different Effects of Estrogen and Progesterone on Experimental Atherosclerosis inFemale Versus Male Rabbits: Quantification of Cellular Proliferation by Bromodeoxyuridine Circulation, July 15, 1996; 94(2): 175 - 181. [Abstract] [Full Text]
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S.-J. Chen, H. Li, J. Durand, S. Oparil, and Y.-F. Chen Estrogen Reduces Myointimal Proliferation After Balloon Injury of Rat Carotid Artery Circulation, February 1, 1996; 93(3): 577 - 584. [Abstract] [Full Text]
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M. Perrot-Applanat, K. Cohen-Solal, E. Milgrom, and M. Finet Progesterone Receptor Expression in Human Saphenous Veins Circulation, November 15, 1995; 92(10): 2975 - 2983. [Abstract] [Full Text]
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G. M. London, A. P. Guerin, B. Pannier, S. J. Marchais, and M. Stimpel Influence of Sex on Arterial Hemodynamics and Blood Pressure : Role of Body Height Hypertension, September 1, 1995; 26(3): 514 - 519. [Abstract] [Full Text]
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