© 1995 American Heart Association, Inc.
Articles |
Effect of 17
-Dihydroequilin Sulfate, a Conjugated Equine Estrogen, and Ethynylestradiol on Atherosclerosis in Cholesterol-Fed Rabbits
From the Department of Pathology (S., J.J., R.W.S.C.), The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC, and the Cardiovascular Diseases and Drug Safety and Metabolism Divisions (S.J.A., A.C.), Wyeth-Ayerst Research, Princeton, NJ.
Correspondence to Richard W. St. Clair, PhD, The Bowman Gray School of Medicine of Wake Forest University, Department of Pathology, Medical Center Blvd, Winston-Salem, NC 27157-1086.
Abstract The effect of 17
-dihydroequilin sulfate (DHES), a
water-soluble estrogen of conjugated estrogens (Premarin), and
ethynylestradiol (EE), a commonly used estrogen found in many oral
contraceptives, on the development of atherosclerosis was studied in
rabbits fed an atherogenic diet (0.2% cholesterol) for 24 weeks. Ten
animals were given 15
µg ·kg-1 · d-1 EE, 10 received
3.8 mg · kg-1 · d-1 of DHES, and the
remaining 10 sham-ovariectomized and 10 ovariectomized animals served
as cholesterol-fed controls. These doses were chosen to have similar
estrogenic potency. Plasma cholesterol concentrations increased to
about 900 mg/dL and did not differ among the experimental groups. After
24 weeks, plasma ß-VLDL and HDL cholesterol concentrations were the
same for all cholesterol-fed groups, while LDL cholesterol was
significantly higher in the two estrogen-treated groups. In spite of
this, both EE and DHES significantly reduced atherosclerosis by 35% in
the aortic arch and 75% to 80% in the thoracic and abdominal aorta.
The reduction in atherosclerosis was seen in animals with a wide range
(400 to 1400 mg/dL) of plasma cholesterol concentrations and was
independent of lipoprotein profile. ß-VLDL isolated from
estrogen-treated animals was not significantly different from control
ß-VLDL in its ability to stimulate cholesterol accumulation in THP-1
macrophages in culture. This suggests that the protective effect of
estrogens on the development of atherosclerosis is not mediated by
qualitative differences in ß-VLDL that affect uptake by macrophages.
The results of this study extend our knowledge of the range of
estrogens that reduce atherosclerosis. Given the lack of effect on
plasma lipid and lipoprotein concentrations, these data are consistent
with the conclusion that estrogens exert some of this beneficial effect
directly at the level of the arterial wall by influencing certain key
components in the pathogenesis of atherosclerosis.
Key Words: estrogens • lipoproteins • macrophages • ß-VLDL • HDL
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