Intercellular Adhesion Molecule (ICAM)-1 and Vascular Cell Adhesion Molecule (VCAM)-1 at the Early Stages of Atherosclerosis in a Rat Model

Backround: Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM-1), participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherosclerosis. The aim of the study was to examine the expression of VCAM-1 and ICAM-1 in the aorta of rats at the early stages of atherosclerosis and the correlation with their plasma concentrations. Materials and Methods: Male rats (n=44), 10 weeks of age, were divided in 4 groups. Groups A and C (n=12) were fed with rich cholesterol diet for 12 and 16 weeks, respectively. Group B (regression group, n=12) was fed for the first 12 weeks with rich cholesterol diet and for another 4 weeks with normal diet. Group D (control group, n=8) was fed with normal diet for 12 weeks. We measured the serum lipid profile, the concentration of soluble ICAM-1 and the immunohistochemical expression of ICAM-1 and VCAM-1 in the endothelium, media and vasa vasorum of the aorta. Results: There were significant differences (p<0.05) in the expression of ICAM-1 between group C (maximum time of rich cholesterol diet) and all other groups in the 3 groups of the aorta studied. There was regression of the expression of ICAM-1 in group B and significant differences (p<0.05) between group B and all the other groups, except group D in the expression of ICAM-1. There were no significant differences in the expression of VCAM-1 between any groups. The serum concentration of soluble ICAM-1 positively correlated with the expression of the molecule in the vasa vasorum (r=0.35, p<0.05) and fibroblasts/smooth muscular cells (r=0.34, p<0.05) of the aorta. Conclusion: A cholesterol diet plays a role in the expression of ICAM-1 but not in that of VCAM-1 in the rat aorta. The expression of ICAM-1 in the aorta regresses after the withdrawal of a cholesterol-rich diet. Soluble ICAM-1 is a reliable measure of ICAM-1 expression in the aorta, vasa vasorum and fibroblasts/smooth muscle cells. Atherosclerosis is influenced by the interactions of cellular adhesion molecules. The cell-surface expression of these molecules in response to pathophysiological stimuli mediates the interaction between the endothelium and blood cells and is central to the development of atherosclerosis (1). Atherosclerosis affects discrete regions of the vasculature, such as vessel curvatures and bifurcations. These regions are characterized by disturbed oscillatory flow that induces up- regulation of proinflammatory adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 (2). Chemokines then stimulate leukocytes and up-regulate α4 and β2 integrin binding to VCAM-1 and ICAM-1 respectively, which themselves mediate later steps (2). VCAM-1 and ICAM-1 are closely related in structure and function. Both are cytokine-inducible Ig gene superfamily members that bind leukocyte integrins (3). We investigated the expression of ICAM-1 and VCAM-1 in the aortic wall of Wistar rats in response to hypercholesterolemia. We also investigated the correlation between the expression of adhesion molecules, the lipid