17 beta-estradiol reduces tumor necrosis factor-alpha-mediated LDL accumulation in the artery wall

Estrogens have direct effects on the vascular wall that may prevent the dev elopment of atherosclerosis, In particular estrogens, such as 17 beta-estra diol (estradiol), are known to have potent antioxidant activity. Tumor necr osis factor-cu (TNF) is found in human atheroma and produces oxygen-derived free radicals, These oxygen-derived free radicals may modify low density l ipoproteins (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-m ediated increase in LDL accumulation be prevented by the antioxidant activi ty 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, a ddition 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 cm(2) vs. 3.38 +/ - 0.48 ng/min per cm(2); P < 0.01). Estradiol (65 pg/ml) and alpha-tocopher ol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indic ating that TNF may exert its effects on LDL accumulation through cellular p roduction of oxygen-derived free radicals.jlr These results support an anti oxidant role for estradiol in the protection against LDL accumulation in th e artery wall and subsequent progression of atherosclerosis.