Intercellular adhesion molecule-1 and vascular endothelial growth factor expression kinetics in macrophage-derived foam cells.
Macrophage-derived foam cells seem to play an important role during inflammatory response of atherosclerosis, in which the overexpression of intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) are associated with the early and later pathological changes in foam cell formation. In this study, we investigated the expression kinetics of ICAM-1 and VEGF in macrophage-derived foam cells. The foam cell model was established through incubating the human monocyte line (U937 cells) with oxidized-low density lipoprotein (ox-LDL). Up-regulated expressions of ICAM-1 and VEGF were analyzed in protein and mRNA levels in U937 foam cells by flow cytometry, ELISA, and Northern blot. Kinetic studies showed the deferent kinds of expression curves in dose response and time course. The expression dose-kinetics demonstrated that the ICAM-1 showed the peak expression induced by ox-LDL 50 mg/L, while VEGF levels increased in a dose-dependent manner with the maximum level induced by ox-LDL 200 mg/L. Time-kinetic studies revealed that the ICAM-1 levels showed the peak expression in 12 h while VEGF expression increased in a time-dependent manner with the maximum level in 48 h. These results proved that both ICAM-1 and VEGF expressions were enhanced in the macrophage-derived foam cells, but ICAM-1 expression increased earlier than the up-regulation of VEGF; low dose of ox-LDL mainly up regulated ICAM-1 expression, while high dose mainly increased the VEGF expression.
Yang
Peng-Yuan
PY
Department of Pharmacology, School of Pharmacy, The Second Military Medical University, 101 Guo He Road, Shanghai 200433, China.
Rui
Yao-Cheng
YC
D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005487:Foam Cells / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D007202:Indicators and Reagents; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases