Original Article

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

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-estradiol (17-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-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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