Reduced neointima hyperplasia of vein bypass grafts in intercellular adhesion molecule-1-deficient mice

Recently, we established a new mouse model of vein graft arteriosclerosis t hrough the grafting of vena cava to carotid arteries. In many respects, the morphological features of this murine vascular graft model resemble those of human venous bypass graft disease. With this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of vein gr aft arteriosclerosis in ICAM-1-deficient mice. Neointimal hyperplasia of ve in grafts in ICAM-1 -/- mice was reduced 30% to 50% compared with that of w ild-type control animals. Immmunofluorescent analysis revealed that increas ed ICAM-1 expression was observed on the endothelium and smooth muscle cell s (SMCs) of the grafted veins in wild-type, but not ICAM-1 -/-, mice. MAC-1 (CD1 11b/18)-positive cells that adhered to the surface of vein grafts in ICAM-1 -/- mice were significantly less as identified with en face immunofl uorescence, and these positive cells were more abundant in the intimal lesi ons of vein grafts in wild-type mice. Furthermore, aortic SMCs cultivated f rom wild-type mice exhibited high ICAM-1 expression in response to tumor ne crosis factor-alpha. When tumor necrosis factor-cr-stimulated SMCs were inc ubated with mouse spleen leukocytes, the number of cells that adhered to IC AM-1 -/- SMCs was significantly lower than the number that adhered to ICAM- 1 +/+ SMCs, which was markedly blocked through pretreatment of leukocytes w ith the anti-MAC-1 antibody. Taken together, our findings demonstrate that ICAM-1 is critical in the development of venous bypass graft arterioscleros is, which provides essential information for therapeutic intervention for v ein graft disease in patients undergoing bypass surgery.