© 1996 American Heart Association, Inc.
Articles |
Native LDL Increases Endothelial Cell Adhesiveness by Inducing Intercellular Adhesion Molecule–1
Presented in part at the 66th American Heart Association Scientific Sessions, Atlanta, Ga, November 8-11, 1993 and published in abstract form (Circulation. 1993;88[pt 2]:I-367).
From the Department of Experimental Pathology (J.H.-C.L., Y.K., M.B.S.), New York Medical College, Valhalla, NY, and the Cardiovascular Research Center and Departments of Pathology (D.M.S., M.L.C., K.A.P.) and Pharmacology and Toxicology (K.A.P.), Medical College of Wisconsin, Milwaukee.
Correspondence to Kirkwood A. Pritchard, Jr, PhD, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226. E-mail kpritch@post.its.mcw.edu.
Abstract Native LDL (n-LDL) increases human umbilical vein endothelial cell (EC) adherence of mononuclear cells. Such phenotypic changes suggest that n-LDL alters the usual expression of cell adhesion molecules to enhance the adhesive properties of the endothelium. To investigate n-LDL mechanisms governing adherence, ECs were exposed to n-LDL in concentrations up to 240 mg/dL for 2 and 4 days. n-LDL–treated ECs bound nearly threefold more phorbol myristate acetate (PMA)–stimulated U937 cells than control ECs but did not bind unstimulated U937 cells. Anti–intercellular adhesion molecule–1 (ICAM-1) antibodies blocked PMA-stimulated U937 cell binding to control and n-LDL–treated ECs by more than 80%, suggesting that increases in ICAM-1 may be involved in this increased adherence. Although increases in PMA-stimulated U937 cell binding developed with respect to time and concentration, statistically significant increases were achieved only when n-LDL concentrations exceeded 180 mg cholesterol/dL at day 4. n-LDL increased endothelial adherence of freshly isolated human monocytes more than twofold and neutrophils by almost twofold. Fluorescent-linked immunoassays revealed that n-LDL increased ICAM-1 protein expression by twofold, which corresponded with increased ICAM-1 message levels. n-LDL also appeared to increase E-selectin and vascular cell adhesion molecule–1 message levels, but these changes did not translate into statistically significant differences in protein levels. Taken together, these data indicate that n-LDL increases ICAM-1 expression to enhance the adhesive properties of the endothelium. Such perturbations in EC function likely represent a proinflammatory response to protracted n-LDL exposure and one of the early steps in atherogenesis.
Key Words: native LDL • intercellular adhesion molecule–1 • E-selectin • vascular cell adhesion molecule–1 • adhesion
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