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The Journal of Lipid Research, Vol. 40, 387-396, March 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

17ß-Estradiol reduces tumor necrosis factor--mediated LDL accumulation in the artery wall

Correspondence to: John C. Rutledge

Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17ß-estradiol (estradiol), are known to have potent antioxidant activity. Tumor necrosis factor- (TNF) is found in human atheroma and produces oxygen-derived free radicals. These oxygen-derived free radicals may modify low density lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated increase in LDL accumulation be prevented by the antioxidant activity of estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and perfused with fluorescently labeled LDL and arterial LDL flux was measured using quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml) to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation (1.50 ± 0.37 ng/min per cm² vs. 3.38 ± 0.48 ng/min per cm²; P < 0.01). Estradiol (65 pg/ml) and -tocopherol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL accumulation through cellular production of oxygen-derived free radicals.

These results support an antioxidant role for estradiol in the protection against LDL accumulation in the artery wall and subsequent progression of atherosclerosis.—Walsh, B.A ., A. E. Mullick, R. L. Walzem, and J. C. Rutledge. 17ß-Estradiol reduces tumor necrosis factor--mediated LDL accumulation in the artery wall. J. Lipid Res. 1999. 40: 387–396.

Supplementary key words: lipoprotein flux, sex hormones, carotid arteries, antioxidants, atherosclerosis

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