Vein graft failure within the first month after bypass surgery is largely because of
thrombosis. However, systemic study of
thrombus formation in vein grafts is still lacking, and few effective techniques are available to prevent this event. Herein, we analyzed the kinetics of
thrombosis and tested the effectiveness of locally applied
aspirin on prevention of the disease in a mouse model. En face analysis of vein grafts revealed that 67+/-12% and 54+/-17% of the surface areas were covered by microthrombi at 1 and 3 days, respectively.
Thrombus generation was also identified by labeling of platelets and
fibrin, which occurred in 35 grafts examined at 1 and 3 days and 1, 2, 4, and 8 weeks. In a fifth of grafts, the
thrombus occluded the vessel lumen by > or =1/4. Furthermore, a significant loss of endothelial cells was evidenced by beta-gal staining for vein grafts in transgenic mice expressing LacZ gene controlled by TIE2-endothelial specific gene promoter. Following
thrombosis, neointimal lesions were significantly increased by 4-fold 2 weeks after the operation. When vein grafts were treated locally with
aspirin in
pluronic gel-127, the
thrombus area was significantly reduced (P<0.005) at 1, 4, and 8 weeks. Interestingly, neointimal lesions were markedly reduced in the local, but not oral,
aspirin-treated group at 4 and 8 weeks by 50% to 70% (P<0.005). The mechanism of reduced lesions by locally applied
aspirin involved the protection of vein graft endothelium. Thus, we provide strong evidence that
thrombus formation occurs before the development of neointimal lesions in vein grafts and that local
aspirin treatment successfully reduces vein graft
arteriosclerosis through endothelial protection, resulting in reduction of
thrombosis.