Expression of intercellular adhesion molecules in human saphenous veins: effects of inflammatory cytokines and neointima formation in culture

Atherosclerosis causes occlusions in as many as 50% of human saphenous Vein coronary artery bypass grafts. Monocyte infiltration is an early step in s aphenous vein-graft atherosclerosis, however, comparatively little is known of its underlying mechanisms. As a first approach, we sought to define the occurrence, location and regulation of leukocyte adhesion molecules in hum an saphenous vein before and after surgical preparation for grafting, durin g neointima formation in culture and on stimulation with inflammatory cytok ines. We compared the distribution of intercellular adhesion molecule (ICAM -1), vascular cell adhesion molecule (VCAM-1) and platelet endothelial cell adhesion molecule (PECAM-1 or CD-31) in endothelial cells and smooth muscl e cells (SMCs), using immunocytochemistry. ICAM-1 was expressed on endothel ial cells before culture and on both endothelial cells and medial or neoint imal SMCs after culturing vein for 14 days in 30% foetal bovine serum or af ter culturing for 24 h with TNF-alpha. Relative tissue levels of ICAM-1 mea sured by Western blotting were significantly elevated by culturing freshly- isolated (0.02 +/- 0.01 to 0.18 +/- 0.03) and surgically-prepared (0.02 +/- 0.01 to 0.14 +/- 0.03; n = 6) veins or following TNF-alpha treatment of su rgically-prepared veins (0.04 +/- 0.01 to 0.32 +/- 0.11, n = 7). VCAM-1 was undetectable before or after culturing but was strongly upregulated on end othelial cells by incubation with the cytokines TNF-alpha, IL-1 alpha or in terferon-gamma. PECAM-1 was expressed constitutively on endothelial cells. We conclude that human saphenous vein expresses several adhesion molecules capable of mediating monocyte migration. The increased expression of ICAM-1 in SMC after culturing or cytokine treatment and of VCAM-1 in endothelial cells suggests that interactions with beta 1 and beta 2 integrins are impor tant pathways for stimulated monocyte ingress into human saphenous vein gra fts. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.