| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Circulation, Vol 89, 2251-2259, Copyright © 1994 by American Heart Association
JF Keaney Jr, GT Shwaery, A Xu, RJ Nicolosi, J Loscalzo, TL Foxall and JA Vita
BACKGROUND: Cardiovascular events are less prevalent in premenopausal women
and women receiving estrogen replacement than in postmenopausal women or
men. Endothelium-derived relaxing factor (EDRF) is an important local
modulator of vascular tone, and abnormal endothelial function is related,
in part, to the oxidative modification of low- density lipoprotein (LDL).
Estrogens possess substantial antioxidant activity and inhibit LDL
modification in vitro. METHODS AND RESULTS: We investigated the effects of
17 beta-estradiol (E2) on endothelial vasomotor function in cholesterol-fed
miniature swine. Animals underwent ovariectomy or a sham procedure and
received E2 or placebo via implant yielding three groups: sham, ovariectomy
(E2 placebo), and implant (E2 implant). After 16 weeks, coronary arteries
were harvested and endothelial function was examined in vitro. Vessels from
the sham and implant groups demonstrated preserved endothelium-dependent
relaxation to bradykinin, substance P, and A23187. Vessels from the
ovariectomy group exhibited impaired relaxation to bradykinin and substance
P (P < .05 versus sham and implant groups) but not to A23187. Plasma E2
levels were strongly correlated with the response to bradykinin (R = .82, P
< .001), substance P (R = .64, P < .01), and A23187 (R = .65, P <
.01). Compared with the ovariectomy group, LDL derived from the sham and
implant groups was markedly resistant to ex vivo oxidation (P < .05),
and this effect correlated with preserved endothelium-dependent relaxation
to bradykinin (R = .62, P < .03) and substance P (R = .61, P < .03).
CONCLUSIONS: Thus, E2 preserves endothelial function in cholesterol-fed
swine in association with protection of LDL against oxidative modification.
These data suggest that E2 may, in part, favorably affect vascular function
and coronary artery disease by virtue of its antioxidant properties.
ARTICLES
17 beta-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine
Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
This article has been cited by other articles:
 |
|
 |
|
  P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Lopez-Sepulveda, R. Jimenez, M. Romero, M. J. Zarzuelo, M. Sanchez, M. Gomez-Guzman, F. Vargas, F. O'Valle, A. Zarzuelo, F. Perez-Vizcaino, et al. Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats Hypertension, April 1, 2008; 51(4): 1088 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Moreau, K. M. Gavin, A. E. Plum, and D. R. Seals Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women Hypertension, June 1, 2005; 45(6): 1107 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Widder, T. Pelzer, C. von Poser-Klein, K. Hu, V. Jazbutyte, K.-H. Fritzemeier, C. Hegele-Hartung, L. Neyses, and J. Bauersachs Improvement of Endothelial Dysfunction by Selective Estrogen Receptor-{alpha} Stimulation in Ovariectomized SHR Hypertension, November 1, 2003; 42(5): 991 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vihma, S. Vehkavaara, H. Yki-Jarvinen, H. Hohtari, and M. J. Tikkanen Differential Effects of Oral and Transdermal Estradiol Treatment on Circulating Estradiol Fatty Acid Ester Concentrations in Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 588 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Cazita, J. A. Berti, C. Aoki, M. Gidlund, L. M. Harada, V. S. Nunes, E. C. R. Quintao, and H. C. F. Oliveira Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice J. Lipid Res., January 1, 2003; 44(1): 33 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Bell, K. E. Gochenaur, and J. Hecht O2--mediated impairment of coronary arterial relaxation is prevented by overnight treatment with 1 nM beta -estradiol J Appl Physiol, December 1, 2002; 93(6): 1952 - 1958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Chambliss and P. W. Shaul Estrogen Modulation of Endothelial Nitric Oxide Synthase Endocr. Rev., October 1, 2002; 23(5): 665 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Darblade, C. Pendaries, A. Krust, S. Dupont, M.-J. Fouque, J. Rami, P. Chambon, F. Bayard, and J.-F. Arnal Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the {alpha}-, but not {beta}-, Estrogen Receptor Circ. Res., March 8, 2002; 90(4): 413 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pendaries, B. Darblade, P. Rochaix, A. Krust, P. Chambon, K. S. Korach, F. Bayard, and J.-F. Arnal The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice PNAS, February 19, 2002; 99(4): 2205 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Dubey, S. Oparil, B. Imthurn, and E. K. Jackson Sex hormones and hypertension Cardiovasc Res, February 15, 2002; 53(3): 688 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Dubey and E. K. Jackson Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms Am J Physiol Renal Physiol, March 1, 2001; 280(3): F365 - F388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hernandez, J. L. Delgado, J. Diaz, T. Quesada, M. J. G. Teruel, M. C. Llanos, and L. F. Carbonell 17beta -Estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1599 - R1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Sbarouni, C Kroupis, Z.S Kyriakides, K Koniavitou, and D.T Kremastinos Cell adhesion molecules in relation to simvastatin and hormone replacement therapy in coronary artery disease Eur. Heart J., June 2, 2000; 21(12): 975 - 980. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Virdis, L. Ghiadoni, S. Pinto, M. Lombardo, F. Petraglia, A. Gennazzani, S. Buralli, S. Taddei, and A. Salvetti Mechanisms Responsible for Endothelial Dysfunction Associated With Acute Estrogen Deprivation in Normotensive Women Circulation, May 16, 2000; 101(19): 2258 - 2263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, T. Esaki, E. Muto, H. Kano, Y. Asai, N. K. Thakur, D. Sumi, M. Jayachandran, and A. Iguchi Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen : The Possible Role of Nitric Oxide Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 782 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Peterson, M. Courtois, L. F. Peterson, M. R. Peterson, V. G. Dávila-Román, R. J. Spina, and B. Barzilai Estrogen Increases Hyperemic Microvascular Blood Flow Velocity in Postmenopausal Women J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2000; 55(3): 174M - 179. [Abstract] [Full Text]
|
|
|
|
|
|
H. Teoh, A. Quan, and R. Y.K Man Acute impairment of relaxation by low levels of testosterone in porcine coronary arteries Cardiovasc Res, March 1, 2000; 45(4): 1010 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhu, B. Bonet, H. Gillenwater, and R. H. Knopp Opposing Effects of Estrogen and Progestins on LDL Oxidation and Vascular Wall Cytotoxicity: Implications for Atherogenesis Experimental Biology and Medicine, December 1, 1999; 222(3): 214 - 221. [Abstract] [Full Text]
|
|
|
|
|
|
O. M. Shapira, A. Xu, G. S. Aldea, J. A. Vita, R. J. Shemin, and J. F. Keaney Jr Enhanced Nitric Oxide-Mediated Vascular Relaxation in Radial Artery Compared With Internal Mammary Artery or Saphenous Vein Circulation, November 9, 1999; 100 (2009): II-322 - II-327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Miyamoto, M. Mandai, I. Suzuma, K. Suzuma, K. Kobayashi, and Y. Honda Estrogen Protects Against Cellular Infiltration by Reducing the Expressions of E-Selectin and IL-6 in Endotoxin-Induced Uveitis J. Immunol., July 1, 1999; 163(1): 374 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mendelsohn and R. H. Karas The Protective Effects of Estrogen on the Cardiovascular System N. Engl. J. Med., June 10, 1999; 340(23): 1801 - 1811. [Full Text] [PDF]
|
|
|
|
|
|
G. Gardner, C. L. Banka, K. A. Roberts, A. E. Mullick, and J. C. Rutledge Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17ß-Estradiol Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 854 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Teoh, S. W.S. Leung, and R. Y.K. Man Short-term exposure to physiological levels of 17{beta}-estradiol enhances endothelium-independent relaxation in porcine coronary artery Cardiovasc Res, April 1, 1999; 42(1): 224 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Walsh, A. E. Mullick, R. L. Walzem, and J. C. Rutledge 17ß-Estradiol reduces tumor necrosis factor-{alpha}-mediated LDL accumulation in the artery wall J. Lipid Res., March 1, 1999; 40(3): 387 - 396. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. Dorup, K. Skajaa, and K. E. Sorensen Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H821 - H825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.A Barbacanne, J Rami, J.B Michel, J.P Souchard, M Philippe, J.P Besombes, F Bayard, and J.F Arnal Estradiol increases rat aorta endothelium-derived relaxing factor (EDRF) activity without changes in endothelial NO synthase gene expression: possible role of decreased endothelium-derived superoxide anion production Cardiovasc Res, March 1, 1999; 41(3): 672 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, Y. Y. Tyurina, V. A. Tyurin, D. G. Gillespie, R. A. Branch, E. K. Jackson, and V. E. Kagan Estrogen and Tamoxifen Metabolites Protect Smooth Muscle Cell Membrane Phospholipids Against Peroxidation and Inhibit Cell Growth Circ. Res., February 5, 1999; 84(2): 229 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Schwenke, J. D. Wagner, and M. R. Adams In vitro lipid peroxidation of LDL from postmenopausal cynomolgus macaques treated with female hormones J. Lipid Res., February 1, 1999; 40(2): 235 - 244. [Abstract] [Full Text]
|
|
|
|
|
|
P. E. Gallagher, P. Li, J. R. Lenhart, M. C. Chappell, and K. B. Brosnihan Estrogen Regulation of Angiotensin-Converting Enzyme mRNA Hypertension, January 1, 1999; 33(1): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gerhard, B. W. Walsh, A. Tawakol, E. A. Haley, S. J. Creager, E. W. Seely, P. Ganz, and M. A. Creager Estradiol Therapy Combined With Progesterone and Endothelium-Dependent Vasodilation in Postmenopausal Women Circulation, September 22, 1998; 98(12): 1158 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. K. Toung, R. J. Traystman, P. D. Hurn, and V. M. Miller Estrogen-Mediated Neuroprotection After Experimental Stroke in Male Rats • Editorial Comment Stroke, August 1, 1998; 29(8): 1666 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ayres, W. Abplanalp, J. H. Liu, and M. T. R. Subbiah Mechanisms involved in the protective effect of estradiol-17beta on lipid peroxidation and DNA damage Am J Physiol Endocrinol Metab, June 1, 1998; 274(6): E1002 - E1008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kleinert, T. Wallerath, C. Euchenhofer, I. Ihrig-Biedert, H. Li, and U. Forstermann Estrogens Increase Transcription of the Human Endothelial NO Synthase Gene : Analysis of the Transcription Factors Involved Hypertension, February 1, 1998; 31(2): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Guetta, A. A. Quyyumi, A. Prasad, J. A. Panza, M. Waclawiw, and R. O. Cannon III The Role of Nitric Oxide in Coronary Vascular Effects of Estrogen in Postmenopausal Women Circulation, November 4, 1997; 96(9): 2795 - 2801. [Abstract] [Full Text]
|
|
|
|
|
|
R. Elhage, F. Bayard, V. Richard, P. Holvoet, N. Duverger, C. Fievet, and J.-F. Arnal Prevention of Fatty Streak Formation of 17ß-Estradiol Is Not Mediated by the Production of Nitric Oxide in Apolipoprotein E– Deficient Mice Circulation, November 4, 1997; 96(9): 3048 - 3052. [Abstract] [Full Text]
|
|
|
|
|
|
R. Elhage, J.-F. Arnal, M.-T. Pieraggi, N. Duverger, C. Fievet, J.-C. Faye, and F. Bayard 17ß-Estradiol Prevents Fatty Streak Formation in Apolipoprotein E–Deficient Mice Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2679 - 2684. [Abstract] [Full Text]
|
|
|
|
|
|
P. Skarsgard, C. Van Breemen, and I. Laher Estrogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2248 - H2256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. White, J. Shelton, S.-J. Chen, V. Darley-Usmar, L. Allen, C. Nabors, P. W. Sanders, Y.-F. Chen, and S. Oparil Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury Circulation, September 2, 1997; 96(5): 1624 - 1630. [Abstract] [Full Text]
|
|
|
|
|
|
S. Brooke, R. Chan, S. Howard, and R. Sapolsky Endocrine modulation of the neurotoxicity of gp120: Implications for AIDS-related dementia complex PNAS, August 19, 1997; 94(17): 9457 - 9462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Shwaery, J. A. Vita, and J. F. Keaney Jr Antioxidant Protection of LDL by Physiological Concentrations of 17ß-Estradiol : Requirement for Estradiol Modification Circulation, March 18, 1997; 95(6): 1378 - 1385. [Abstract] [Full Text]
|
|
|
|
|
|
K. K. Koh, R. Mincemoyer, M. N. Bui, G. Csako, F. Pucino, V. Guetta, M. Waclawiw, and R. O. Cannon Effects of Hormone-Replacement Therapy on Fibrinolysis in Postmenopausal Women N. Engl. J. Med., March 6, 1997; 336(10): 683 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oparil, R. L. Levine, S.-J. Chen, J. Durand, and Y.F. Chen Sexually Dimorphic Response of the Balloon-Injured Rat Carotid Artery to Hormone Treatment Circulation, March 4, 1997; 95(5): 1301 - 1307. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. L. Hale, Y. Birnbaum, and R. A. Kloner Estradiol, Administered Acutely, Protects Ischemic Myocardium in Both Female and Male Rabbits Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(1): 47 - 52. [Abstract] [PDF]
|
|
|
|
|
|
M. R. Adams, T. C. Register, D. L. Golden, J. D. Wagner, and J. K. Williams Medroxyprogesterone Acetate Antagonizes Inhibitory Effects of Conjugated Equine Estrogens on Coronary Artery Atherosclerosis Arterioscler Thromb Vasc Biol, January 1, 1997; 17(1): 217 - 221. [Abstract] [Full Text]
|
|
|
|
|
|
Y. D. Kim, B. Chen, J. Beauregard, P. Kouretas, G. Thomas, M. Y. Farhat, A. K. Myers, and D. E. Lees 17ß-Estradiol Prevents Dysfunction of Canine Coronary Endothelium and Myocardium and Reperfusion Arrhythmias After Brief Ischemia/Reperfusion Circulation, December 1, 1996; 94(11): 2901 - 2908. [Abstract] [Full Text]
|
|
|
|
|
|
S. Taddei, A. Virdis, L. Ghiadoni, P. Mattei, I. Sudano, G. Bernini, S. Pinto, and A. Salvetti Menopause Is Associated With Endothelial Dysfunction in Women Hypertension, October 1, 1996; 28(4): 576 - 582. [Abstract] [Full Text]
|
|
|
|
|
|
V. Guetta and R. O. Cannon III Cardiovascular Effects of Estrogen and Lipid-Lowering Therapies in Postmenopausal Women Circulation, May 15, 1996; 93(10): 1928 - 1937. [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Gerhard and P. Ganz How Do We Explain the Clinical Benefits of Estrogen? : From Bedside to Bench Circulation, July 1, 1995; 92(1): 5 - 8. [Full Text]
|
|
|
|
|
|
B. Darblade, C. Pendaries, A. Krust, S. Dupont, M.-J. Fouque, J. Rami, P. Chambon, F. Bayard, and J.-F. Arnal Estradiol Alters Nitric Oxide Production in the Mouse Aorta Through the {alpha}-, but not {beta}-, Estrogen Receptor Circ. Res., March 8, 2002; 90(4): 413 - 419. [Abstract] [Full Text] [PDF]
|
|