Effects of gene transfection on the intimal thickening of the autogeneous vein grafts

内皮衍生的松弛因子被确认为一氧化氮(NO)，它不仅是一种血管扩张剂，而且还能抑制血小板聚集、黏附和血管平滑肌的增殖。然而，关于自体静脉移植物的这种内皮功能的信息很少。结果：1)在血流条件较差的犬移植静脉中，血管内膜明显增厚，对ADP和凝血酶的内皮依赖性松弛功能受损，ACh诱导的血管内皮依赖性松弛功能受损。2)长期给予饲料中的L-精氨酸可减轻高胆固醇血症兔颈总静脉移植物的内膜增厚。3)在贫血流下，将含有牛ecNOS基因或对照载体的脂质体植入犬自体静脉移植物内。移植后4周，ecNOS组移植静脉内膜增厚程度明显低于载体组。结论：移植静脉内皮细胞NO的生成明显受损。这种内皮功能障碍可能会加速移植静脉的内膜增厚，并导致晚期移植失败。保存或增加自体静脉移植物内皮细胞中NO的产生可能有利于防止移植物晚期衰竭。这种基因转移值得进一步研究，作为预防晚期移植失败的一种可能方法。

The endothelium-derived relaxing factor, which has been identified as nitric oxide(NO) is not only a vasodilator but also inhibits platelet aggregation, adherence and vascular smooth muscle proliferation. However, little information is available on such endothelial functions of autogenous vein grafts. Therefore, the endothelium-dependent and -independent responses were examined in the unoperated vein and vein grafts by organ chambers for isometric tension recordingResults : 1) In the canine vein grafts under poor runoff conditions, which had pronounced intimal thickening, the endothelium-dependent relaxations to ADP and thrombin are impaired, in addition to the impaired ACh-induced responses. 2 ) Intimal thickening of rabbit juglar vein grafts under hypercholesterolemia was reduced by chronic administration of dietary L-arginine, which is a precursor of nitric oxide by enhancing the NO production of the endothelium. 3 ) HVJ-liposomes containing encapsulated bovine ecNOS cDNA or control vector plasmid was implanted into the canine autogenous vein grafts under poor runoff. At four weeks after, the average value of intimal thickening was significantly reduced by ecNOS in comparison with vector group.Conclusions : These results suggest that the production of NO in the endothelium of the vein grafts was significantly impaired. This dysfunction of the endothelium may accelerate intimal thickening of the vein graft and result in late graft failure. The preservation or enhancement of NO production in the endothelium of the autogenous vein grafts may be beneficial for preventing the late graft failure. The gene transfer warrants further study as a possible approach to prevent late graft failure.