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J. Lipid Res.
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The Journal of Lipid Research, Vol. 40, 893-900, May 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice

Marion M. Marsha, V. Robert Walkera, Linda K . Curtissa,b, and Carole L. Bankaa
a Department of Immunology, The Scripps Research Institute, La Jolla, CA, 92037
b Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA, 92037

Correspondence to: Marion M. Marsh

Low density lipoprotein (LDL) receptor-deficient (LDLR-/-) mice consuming a high fat diet were used to assess the effect of endogenous and exogenous estradiol (E2) on atherosclerosis. Sexually mature female mice were ovariectomized (OVX) and implanted with subcutaneous, slow-release pellets designed to release 6 µg/day of exogenous 17ß-estradiol (17ß-E2 ), 17{alpha}-estradiol (17{alpha}-E2 ), or placebo (E2- deficient). Sham-operated control female (endogenous E2 ) and male mice were studied as controls. Aortic atherosclerotic lesion area was reduced by physiologic amounts of both endogenous and exogenous E2 compared to E2-deficient female mice. Although plasma cholesterol levels were reduced by exogenous E2 despite the absence of the LDL receptor, endogenous E2 was not associated with any cholesterol changes. In contrast, only 17{alpha}-E2 was associated with decreased fasting triglyceride.

In subgroup analyses matched for time-averaged plasma total cholesterol, aortic lesion area was reduced by the presence of estradiol (E2 ). E2 protected LDLR-/- female mice from atherosclerosis and this protection was independent of changes in plasma cholesterol levels.—Marsh, M. M., V. R. Walker, L. K . Curtiss, and C. L. Banka. Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice. J. Lipid Res. 1999. 40: 893–900.

Supplementary key words: estradiol, estrogen, atherosclerosis, cholesterol, triglyceride, LDL receptor-deficient mice, mouse model, hormone replacement therapy, cervical carcinoma


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