Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation

The recruitment of mononuclear leukocytes and formation of intimal macropha ge-rich lesions at specific sites of the arterial tree are key events in at herogenesis. Inducible endothelial cell adhesion molecules may participate in this process. In aortas of normal chow-fed wild-type mice and rabbits, v ascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecu le-1 (ICAM-1), but not E-selectin, were expressed by endothelial cells in r egions predisposed to atherosclerotic lesion formation. En face confocal mi croscopy of the mouse ascending aorta and proximal arch demonstrated that V CAM-1 expression was increased on the endothelial cell surface in lesion-pr one areas. ICAM-1 expression extended into areas protected from lesion form ation. Hypercholesterolemia induced atherosclerotic lesion formation in rab bits, LDL receptor and apolipoprotein E knockout mice, and Northern blot an alysis demonstrated increased steady-state mRNA levels of VCAM-1 and ICAM-1 , but not of E-selectin. Immunohistochemical staining revealed that VCAM-1 and ICAM-1 were expressed predominantly by endothelium in early lesions and by intimal cells in more advanced lesions. In early and advanced lesions, staining was most intense in endothelial cells at and adjacent to lesion bo rders. ICAM-1 staining extended into the uninvolved aorta. These expression patterns were highly reproducible in both species, The only difference was that VCAM-1 expression in endothelium over the central portions of lesions was found frequently in rabbits and rarely in mice. The expression of VCAM -1 by arterial endothelium in normal animals may represent a pathogenic mec hanism or a phenotypic marker of predisposition to atherogenesis.