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 kappa B (NF-kappa 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-kappa 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-kappa B.