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

晚期移植物失效仍然是一个严重的问题，特别是在有较差的流出(低剪应力)血管的情况下。我们已经报道，自体静脉移植物在不良血流模型中的内膜增厚显著高于正常血流模型组。内皮通过释放前列环素或内皮衍生的松弛因子-一氧化氮(NO)-GT；来调节基础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因子。本实验采用不良径流模型，研究犬自体静脉移植物在不良径流条件下，前列环素和一氧化氮的产生是否发生改变。在以低切应力为特征的异常血流状态下，犬静脉移植物中前列环素的产生低于正常血流状态。此外，犬静脉移植物中NO的产生在恶劣的径流条件下也受到损害。海洋油和高水平的二十碳五酸(EPA)阻止了静脉移植物的内膜增厚。然而，EPA阻止内膜增厚的确切机制仍不清楚。本实验旨在研究补充EPA是否会改变犬逆行静脉移植物中NO的产生。这些结果表明，补充EPA减少了自体静脉移植物的内膜增厚，这可能是由于促进了NO的释放。这些结果表明，在异常血流条件下，内皮功能障碍，即前列环素或NO的产生减少，可能因此增加了血小板聚集，最终促进了周围动脉闭塞性疾病的发展，从而导致晚期移植物失败的发生。内皮功能的保护或增强可能是预防移植物晚期衰竭的重要机制。

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.