NATIVE LDL INCREASES ENDOTHELIAL-CELL ADHESIVENESS BY INDUCING INTERCELLULAR-ADHESION MOLECULE-1

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 enhan ce the adhesive properties of the endothelium. To investigate n-LDL me chanisms governing adherence, ECs were exposed to n-LDL in concentrati ons up to 240 mg/dL for 2 and 4 days. n-LDL-treated ECs bound nearly t hreefold more phorbol myristate acetate (PMA)-stimulated U937 cells th an control ECs but did not bind unstimulated U937 cells. Anti-intercel lular adhesion molecule-1 (ICAM-1) antibodies blocked PMA-stimulated U 937 cell binding to control and n-LDL-treated ECs by more than 80%, su ggesting that increases in ICAM-1 may be involved in this increased ad herence. Although increases in PMA-stimulated U937 cell binding develo ped 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 fre shly isolated human monocytes more than twofold and neutrophils by alm ost twofold. Fluorescent-linked immunoassays revealed that n-LDL incre ased ICAM-1 protein expression by twofold, which corresponded with inc reased ICAM-1 message levels. n-LDL also appeared to increase E-select in and vascular cell adhesion molecule-1 message levels; but these cha nges did not translate into statistically significant differences in p rotein levels. Taken together, these data indicate that n-LDL increase s ICAM-1 expression to enhance the adhesive properties of the endothel ium. Such perturbations in EC function likely represent a proinflammat ory response to protracted n-LDL exposure and one of the early steps i n atherogenesis.