Monocyte adhesion to human vein grafts: A marker for occult intraoperative injury?

dObjective: Monocyte adhesion to the vessel wall is believed to be an important initiating event in atherosclerosis and intimal hyperplasia. We hypothesized that occult intraoperative vein injury induces an immediate increase in monocyte adhesion that may be critical to the development of vein graft disease. Methods: Vein segments were obtained from patients (n = 23) undergoing lower extremity bypass. The initial segment (V1, n = 17) was excised immediately at the time of conduit harvest. A second segment (V2, n = 23) was obtained from the distal conduit just before performing the distal anastomosis. Segments were incubated with radiolabeled THP-1 cells (monocytoid cell line) for 1 hour at 37 degreesC, then rinsed and solubilized for determination of bound radioactivity. In a subset of grafts (n = 4), THP-1 cells were preincubated with monoclonal antibody (mAB) 7E3 (which binds to the monocyte integrin Mac-1 at its fibrinogen [Fg]-binding site) or control (mAB 14E11). Fg deposition and endothelial coverage were. evaluated by immunohistochemistry (n = 10). Statistical analysis was performed using the paired t test and analysis of variance. Follow-up graft patency data were obtained and correlated with adhesion values using an exact test (StatXact, Cytel Software, Cambridge, Mass). Results. Monocyte adhesion was significantly increased after surgical manipulation (V1, 2400 +/- 770 versus V2, 7343 +/- 1555 cells/cm(2); P < .02). Fg deposition was abundant in V2 sections and not seen in Vl. Monocyte adhesion to V2 segments was significantly reduced (58% of control, P < .01) by 7E3 treatment. Graft follow-up was complete with a mean interval of 11 months. Higher V2 adhesion values were associated with occluded grafts (P = .07). The median value for the six occluded grafts was 6234 cells/cm(2) versus 3892 cells/cm(2) for the 17 patent grafts. Conclusions. Monocyte adhesion to the vein wall is immediately increased after surgical manipulation and is inhibited by mAB 7E3. Early monocyte adhesion to vein grafts is likely to involve interactions between Mac-1 and Pg. Heightened levels of monocyte adhesion at implantation may be a marker for subsequent vein graft failure.