In vivo low-density lipoprotein exposure induces intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 correlated with activator protein-1 expression.
OBJECTIVE
We tested the hypothesis that direct native low-density lipoprotein (LDL) injection into LDL receptor-deficient (LDLR(-/-)) mice would induce the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in their aortic endothelial cells, and that transcriptional regulation of this pathway involved activator protein-1 (AP-1) but not nuclear factor kappaB (NF-kappaB).


RESULTS
Using tail vein injection of LDL into LDLR(-/-) mice, we were able to maintain atherogenic LDL blood levels, which induced ICAM-1 and VCAM-1 expression in their aortic endothelial cells after 24 hours. We were able to visualize and quantify this expression using immunohistochemistry and confocal microscopy. Under conditions in which ICAM-1 and VCAM-1 were expressed, the regulatory AP-1 proteins c-Fos and c-Jun were also highly expressed in the endothelial cell cytoplasm and observed within the cell nucleus. The NF-kappaB protein P65, although expressed in the endothelial cell cytoplasm after LDL injection, was not observed within the cell nucleus.


CONCLUSIONS
Elevated LDL blood levels, maintained in vivo, increased the expression of the adhesion molecules ICAM-1 and VCAM-1 in aortic endothelial cells. This effect appeared to correlate with AP-1 but not NF-kappaB.
Verna
Lynne
L
Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA. lynne.verna@ucr.edu
Ganda
Chintya
C
Stemerman
Michael B
MB
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism*; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D002352:Carrier Proteins; D008077:Lipoproteins, LDL; D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; C498144:Rela protein, mouse; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D048031:JNK Mitogen-Activated Protein Kinases