Native LDL increases endothelial cell adhesiveness by inducing intercellular adhesion molecule-1.
Native LDL (n-LDL) increased 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-cellular 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.
Smalley
D M
DM
Department of Experimental Pathology, New York Medical College, Valhalla, NY. USA.
Lin
J H
JH
Curtis
M L
ML
Kobari
Y
Y
Stemerman
M B
MB
Pritchard
K A
KA
D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000502:physiology*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008077:Lipoproteins, LDL; D015335:Molecular Probes; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate