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

基因转染对自体静脉移植物内膜增厚的影响

基本信息

批准号：
08671375
负责人：
KOMORI Kimihiro
金额：
$ 1.6万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671375/
关键词：
Nitric oxide Vein grafts poor runoff arginine HVJ-liposome 異常血流

项目摘要

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.

内皮源性舒张因子已被确定为一氧化氮（NO），它不仅是一种血管扩张剂，而且还能抑制血小板聚集、粘附和血管平滑肌增殖。然而，关于自体静脉移植物的内皮功能的信息很少。因此，通过器官室检查未手术静脉和静脉移植物中的内皮依赖性和非依赖性反应，进行等长张力记录结果：1）在径流条件差的犬静脉移植物中，内膜明显增厚，内皮依赖性松弛除了 ACh 诱导的反应受损外，ADP 和凝血酶的功能也受损。 2)通过长期给予膳食L-精氨酸，可以减少高胆固醇血症下兔颈静脉移植物的内膜增厚，L-精氨酸是通过增强内皮NO产生而产生一氧化氮的前体。 3)将含有封装的牛ecNOS cDNA或对照载体质粒的HVJ-脂质体在差径流下植入犬自体静脉移植物中。 4周后，与载体组相比，ecNOS的内膜增厚平均值显着降低。结论：这些结果表明静脉移植物内皮细胞中NO的产生显着受损。这种内皮功能障碍可能会加速静脉移植物的内膜增厚并导致晚期移植物失败。自体静脉移植物内皮细胞中 NO 生成的保存或增强可能有利于预防晚期移植物失败。基因转移值得进一步研究，作为预防晚期移植失败的可能方法。