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.
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|
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|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
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 |
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|
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|
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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]
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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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