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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:854-861.)
© 1999 American Heart Association, Inc.

Original Contributions

Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17ß-Estradiol

Gerrie Gardner; Carole L. Banka; Kim A. Roberts; Adam E. Mullick; John C. Rutledge

From the Division of Cardiovascular Medicine, University of California, Davis (G.G., K.A.R., A.E.M., J.C.R.), and The Scripps Research Institute (C.L.B.), La Jolla, Calif.

Correspondence to John C. Rutledge, MD, Division of Cardiovascular Medicine, One Sheilds Drive, TB 172, University of California, Davis, CA 95616. E-mail jcrutledge{at}ucdavis.edu

Abstract—Current research suggests that estrogen may have primary effects on the artery wall. To investigate the mechanisms of female sex hormone actions in the artery wall, we used an isolated, perfused, rat carotid artery model to examine the effects of estradiol on the rates of accumulation of normal (N-LDL) and minimally modified (MM-LDL) low density lipoprotein in ovariectomized rats. N-LDL, MM-LDL, and oxidized LDL (OX-LDL) were fluorescently labeled and perfused into individual arteries. The rate of LDL accumulation was measured by quantitative fluorescence microscopy before and after treatment with estradiol (1 nmol/L, 272 pg/mL). Estradiol had no effect on the rate of N-LDL accumulation (45±12 versus 48±15 ng cholesterol per cm² per h). However, estradiol significantly decreased the rate of MM-LDL (240±48 versus 160±48 ng cholesterol per cm² per h; P<0.05) and OX-LDL (191±53 versus 112±36 ng cholesterol per cm² per h; P<0.05) accumulation. Further experiments showed that perfusion of unlabeled MM-LDL (100 µg/mL) increased endothelial layer permeability when the rate of accumulation of a water-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 cm² per h, n=6 arteries; P<0.05). Estradiol prevented the expected increase in the rate of dextran accumulation when perfused with MM-LDL (control, 415±49 ng per cm² per h and MM-LDL+estradiol, 415±160 ng per cm² per h). Our studies show that estradiol prevents compromise of the endothelial barrier mediated by MM-LDL and attenuates accumulation of MM-LDL in the artery wall.

Key Words: artery • arteriosclerosis • LDL • estrogen • oxidized LDL • endothelium • permeability

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