Effects of shear stress on the intimal hyperplasia of autogenous Vein grafts

晚期移植失败仍然是一个重要的问题，特别是在径流差（低剪切应力）血管的情况下。我们已经报道了差流模型自体静脉移植物的内膜增厚明显大于正常血流组。内皮通过释放前列环素或内皮源性松弛因子<一氧化氮(NO) >来调节血管平滑肌的反应性。这些因子不仅是血管扩张剂，而且是血小板聚集的有效抑制剂。本实验旨在通过不良径流模型研究犬自体静脉移植在不良径流条件下是否会改变前列环素或一氧化氮的产生。在以低剪切应力为特征的异常血流条件下，犬静脉移植物的前列环素产量低于正常血流条件下。此外，在径流条件差的情况下，犬静脉移植物一氧化氮的产生也受到损害。海洋油和高水平的二十碳五烯酸（EPA）可以防止静脉移植物的内膜增厚。然而，EPA防止内膜增厚的确切机制尚不清楚。本实验旨在研究补充EPA是否会改变狗逆行静脉移植中NO的产生。本研究结果表明，补充EPA可减少自体静脉移植物的内膜增厚，这可能是由于一氧化氮释放的改善。这些结果提示，在异常血流条件下，内皮功能障碍，如前列环素或NO的产生减少，从而可能增加血小板聚集，最终促进外周动脉闭塞性疾病的发展，从而发生晚期移植物衰竭。内皮功能的维持或增强可能是预防晚期移植物衰竭的重要手段。

Late graft failure is still a significant problem particularly in cases with poor runoff (low shear stress) vessels. We have already reported that the intimal thickening of the autogenous vein graft in the poor runoff model was significantly thicker than that in normal flow group. Endothelium modulates the responsiveness of the underlying vascular smooth muscles by releasing prostacyclin or endothelium-derived relaxing factor <Nitric Oxide (NO) >. These factor are not only vasodilators but also potent inhibitors of platelet aggregation. The present experiments were desingned to examine whether the production of prostacyclin or NO were altered in poor runoff conditions of canine autogenous vein grafts by using a poor runoff model. Under abnormal flow conditions characterized by low shear stress, the production of prostacyclin in the canine vein graft was lower than that in normal flow conditions. In addition, the production of NO in canine vein grafts are also impaired under poor runoff conditions.Marine oils and high levels of eicosapentanoic acid (EPA) prevents intimal thickening in vein grafts. However, the precise mechanism by which EPA prevents intimal thickening is still unknown. The present experiments was designed toexamine whether EPA supplementation would alter the NO production in reversed vein grafts of dogs. The presents results demonstrated that EPA supplementation reduces intimal thickening of the autogenous vein graft, which may be due to an improved release of NO.These results suggest that the dysfunction of the endothelium in terms of the decreased production of prostacyclin or NO under abnormal flow conditions may thus increase platelet aggregation and eventually facilitate the development of peripheral arterial occlusive disease and thus the occurrence of late graft failure. The preserved or enhanced endothelial function may be important role for preventing the late graft failure.