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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1344.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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; Chintya Ganda; Michael B. Stemerman

From the Division of Biomedical Sciences, University of California, Riverside.

Correspondence to Lynne Verna, Division of Biomedical Sciences, B650 Statistics Rd, University of California, Riverside, CA 92521. 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.

Injection of LDL into LDLR^–/– mice increased the expression of ICAM-1 and VCAM-1 in their aortic endothelial cells. At the same time, the transcription factor AP-1 proteins c-Jun and c-Fos, but not the NF-B protein P65, were observed within the aortic endothelial cell nucleus. This indicated that AP-1, but not NF-B, was correlated with adhesion molecule expression in response to elevated blood LDL levels.

Key Words: atherosclerosis • endothelium • low-density lipoprotein • AP-1 • NF-B

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