Modified LDL-mediated increases in endothelial layer permeability are attenuated with 17 beta-estradiol

Current research suggests that estrogen may have primary effects on the art ery wall. Td investigate the mechanisms of female sex hormone actions in th e artery wall, we used an isolated, perfused, rat carotid artery model to e xamine the effects of estradiol on the rates of accumulation of normal (N-L DL) and minimally modified (MM-LDL) low density lipoprotein in ovariectomiz ed rats. N-LDL, MM-LDL, and oxidized LDL (OX-LDL) were fluorescently labele d and perfused into individual arteries. The rate of LDL accumulation was m easured by quantitative fluorescence microscopy before and after treatment with estradiol (1 nmol/L, 272 pg/mL). Estradiol had no effect on the rate o f N-LDL accumulation (45+/-12 versus 48+/-15 ng cholesterol per cm(2) per h ). However, estradiol significantly decreased the rate of MM-LDL (240+/-48 versus 160+/-48 ng cholesterol per cm(2) per h; P<0.05) and OX-LDL (191+/-5 3 versus 112+/-36 ng cholesterol per cm(2) per h; P<0.05) accumulation. Fur ther experiments showed that perfusion of unlabeled MM-LDL (100 mu g/mL) in creased endothelial layer permeability when the rate of accumulation of a w ater-soluble, fluorescently labeled, reference molecule (64 000 -molecular weight dextran) was determined before and after perfusion of MM-LDL (319+/- 96 versus 510+/-191 ng per cm(2) per h, n=6 arteries; P<0.05). Estradiol pr evented the expected increase in the rate of dextran accumulation when perf used with MM-LDL (control, 415+/-49 ng per cm(2) per h and MM-LDL+estradiol , 415+/-160 ng per cm(2) per h). Our studies show that estradiol prevents c ompromise of the endothelial barrier mediated by MM-LDL and attenuates accu mulation of MM-LDL in the artery wall.