Partial prevention of monocyte and granulocyte activation in experimental vein grafts by using a biomechanical engineering approach

Leukocytes interact with endothelial cells and contribute to the developmen t of vascular diseases such as thrombosis and atherosclerosis. These proces ses are possibly influenced by mechanical factors. This study focused on th e role of mechanical stretch in the activation of monocytes and granulocyte s in experimental vein grafts. Two models were created by using rats: a non engineered vein graft with increased tensile stress, which was created by g rafting a jugular vein into the abdominal aorta, and an engineered vein gra ft with reduced tensile stress. which was created by restricting the vein g raft into a cylindrical sheath constructed by using fixative-treated intest inal tissue. The density of activated monocytes and granulocytes, which att ached to the endothelium, and the distribution of the intercellular adhesio n molecule (ICAM)-1 in endothelial cells were examined using immunohistolog ical assays. It was found that: in nonengineered vein grafts, the density o f activated monocytes and granulocytes increased significantly compared to that in normal jugular veins at day 1, 5, 10 and 30. At each observation ti me, the cell density in the proximal region of the nonengineered vein graft s was significantly higher than that in the middle and distal regions, and the cell density in the distal region was significantly higher than that in the middle region. These changes were associated with ICAM-1 clustering at day 1 and 5 and focal ICAM-1 un-regulation at day 10 and 20. In engineered vein grafts, the density of activated monocytes and granulocytes decreased significantly compared to that in nonengineered vein grafts at all observa tion times, although it was significantly higher than that in normal jugula r veins. At each observation time, the cell density in the proximal and dis tal regions was significantly higher than that in the middle region, but no significant difference was found between the proximal and distal regions. ICAM-1 clustering along endothelial cell borders was found at day 1 and 5, but no apparent focal ICAM-1 up-regulation was found at day 10 and 20. Thes e results suggested that mechanical stretch due to exposure to increased te nsile stress contributed to the activation of monocytes and granulocytes in experimental vein grafts, and this event could be partially prevented by r educing tensile stress usings a biomechanical engineering approach. (C) 199 9 Elsevier Science Ltd. All rights reserved.