Thrombosis and Neointima Formation in Vein Grafts Are Inhibited by Locally Applied Aspirin Through Endothelial Protection

Abstract

Abstract-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 67Ϯ12% and 54Ϯ17% 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 Ն1/4. Furthermore, a significant loss of endothelial cells was evidenced by ␤-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 (PϽ0.005) 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% (PϽ0.005). 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.

A new systolic parameter defined as the ratio of brachial pre-ejection period to brachial ejection time predicts overall and cardiovascular mortality in hemodialysis patients

“…[23][24][25][26] Hemodialysis patients are usually prescribed many of these medications for cardiovascular causes. In this study, patients in the mortality group had a higher percentage of having received aspirin or ACEI and/or ARB therapy.…”

Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration

“…The close relation between thrombus formation and neointima hyperplasia is suggested in vein graftinduced intimal hyperplasia (27), and stent thrombosis has been a serious concern after coronary stenting (28). It has been shown that thrombi induce inflammatory cell accumulation and cytokine release that may perturb the structural integrity within the aneurysm (29).…”

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

“…Recent advances in the understanding of neovascularisation have made angiogenesis a prime target for therapeutic manipulation in wound healing. Efforts have been made to induce or stimulate new blood vessel formation in order to reduce the unfavourable tissue effects caused by local ischaemia or to enhance tissue repair 6,7,8 . Growth factors, which are now known to participate in cell division, migration, differentiation, and enzyme production, are also important regulators of wound angiogenesis 9,10 .…”

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