Low-density lipoprotein induces vascular adhesion molecule expression on human endothelial cells.
We tested the hypothesis that low-density lipoprotein (LDL) and its acetylated form influence surface expression of vascular adhesion molecules on human endothelial cells. Vascular adhesion molecule surface expression was assessed with flow cytometry on cultured endothelial cells with a modified enzyme-linked immunosorbent assay. LDL acetylation was determined by chromatography. Monocyte adhesion to endothelial cells was assessed with U937 cells by direct counting. Tumor necrosis factor-alpha (10 ng/mL), a positive control, induced a time-dependent expression of vascular adhesion molecules (P < .05), which peaked at 5 hours. Incubation of endothelial cells with LDL (1.3 to 26.0 mmol/L) led to an increase in expression at 2 and 5 hours (P < .05). Prolonged (24-hour) exposure to LDL resulted in a second peak. The effect of acetylated LDL on expression was not different from that of native LDL. Incubation with the protein kinase C inhibitor staurosporine (5 x 10(-8) mol/L) blocked the effects of both native and acetylated LDL completely (P < .05). The calcium channel blocker nitrendipine (10(-7) mol/L) did not influence the expression of vascular adhesion molecule at 2 and 5 hours but did reduce the effect of LDL on expression at 24 hours. LDL (2.6 mmol/L) also induced a significant increase in the surface expression of intercellular adhesion molecule-1 but did not affect the expression of endothelial adhesion molecules. LDL (2.6 mmol/L) induced a significant increase in monocyte binding. We conclude that LDL can induce the expression of vascular adhesion molecules on endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Haller
H
H
Franz Volhard Clinic, Berlin, Germany.
Schaper
D
D
Ziegler
W
W
Philipp
S
S
Kuhlmann
M
M
Distler
A
A
Luft
F C
FC
D002121:Calcium Channel Blockers / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D002121:Calcium Channel Blockers; D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C032629:acetyl-LDL; D011493:Protein Kinase C