Induction of vascular cell adhesion molecule-1 by low-density lipoprotein.
Low-density lipoprotein (LDL) is a well-established risk factor for atherosclerosis. When endothelial cells are incubated with this lipoprotein in pathophysiologic amounts, the cells are activated. Among the documented cellular responses to LDL is increased recruitment of monocytes, which are believed to play a major role in promoting intimal plaque formation. The findings presented here link an atheogenic lipoprotein, LDL, with the induction of an adhesion molecule important in atherogenesis Human LDL induces the vascular cell adhesion molecule-1 (VCAM-1) transcriptionally with an increase in mRNA levels through activation of the VCAM promoter. This effect is blocked by anti-VCAM antibodies. After a 2-day incubation in LDL, the binding of NF-kappa B, which is believed to be a key oxidative-stress sensor for VCAM regulation, remains at basal level. In contrast, the binding activities of AP-1 and GATA, on the other hand, are increased by LDL. Thus, a component of LDL-enhanced endothelial recruitment of monocytes is attributed to VCAM-1 expression, which appears to be mediated through AP-1 and GATA. These data identify LDL as a VCAM-inducer possibly distinct from cytokines and endotoxin.
Lin
J H
JH
Department of Pathology, New York Medical College, Valhalla 10595, USA.
Zhu
Y
Y
Liao
H L
HL
Kobari
Y
Y
Groszek
L
L
Stemerman
M B
MB
D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D050989:GATA2 Transcription Factor; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D016207:Cytokines; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1