Effect of 17 alpha-dihydroequilin sulfate, a conjugated equine estrogen, and ethynylestradiol on atherosclerosis in cholesterol-fed rabbits.

Abstract

The effect of 17 alpha-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 micrograms. 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 beta-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. beta-VLDL isolated from estrogen-treated animals was not significantly different from control beta-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 beta-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.

• Authors: Sulistiyani, S J Adelman, A Chandrasekaran, J Jayo, R W St Clair
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 15 Issue 7 Pg. 837-46 (Jul 1995) ISSN: 1079-5642 [Print] United States
• PMID: 7600114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, Dietary
• Cholesterol, HDL
• Lipoproteins, VLDL
• Triglycerides
• Equilin
• 17-dihydroequilin 3-sulfate
• Ethinyl Estradiol
• Cholesterol

Topics

• Animals
• Aorta (chemistry, pathology)
• Arteriosclerosis (etiology, pathology, prevention & control)
• Cholesterol (analysis, blood)
• Cholesterol, Dietary (administration & dosage)
• Cholesterol, HDL (blood)
• Equilin (analogs & derivatives, blood, therapeutic use)
• Ethinyl Estradiol (blood, therapeutic use)
• Female
• Lipoproteins, VLDL (blood)
• Ovariectomy
• Rabbits
• Triglycerides (blood)