17-estradiol reduces tumor necrosis factor--mediated LDL accumulation in the artery wall
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abstract
Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17- 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.
