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.