on April 13, 2006
Published online before print April 13, 2006, doi: 10.1161/01.ATV.0000222152.83069.3f
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Submitted on September 6, 2005
Accepted on March 17, 2006
In Vivo Low-Density Lipoprotein Exposure Induces Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Correlated With Activator Protein-1 Expression
Lynne Verna *;
From the Division of Biomedical Sciences, University of California, Riverside.
* To whom correspondence should be addressed. E-mail: lynne.verna{at}ucr.edu.
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 
B (NF-B).
Methods and 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-B 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-B.
Key words: atherosclerosis • endothelium • low-density lipoprotein • AP-1 • NF-
B
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