ウサギ移植自家静脈グラフト内膜肥厚と内皮機能

―Nitric Oxideと遺伝子治療―

抄録

Late graft failure of autogenous vein grafts is a critical problem, particularly in the presence of poor runoff vessels. Intimal hyperplasia is considered to be the main cause of graft failure.
The 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. We examined to clarify the relationship between the vein graft intimal thickening and NO.
Results: 1) In rabbit jugular vein grafts, Acetylcholine (ACh)-induced endothelium-dependent relaxations and ACh-induced endothelium-mediated production of c-GMP were significantly impaired compared to those of control vein, while SIN-I(the active metabolite of molsidomine)-induced relaxations and production of c-GMP were comparable between the two groups. 2) Hypercholesterolemia accelerated the intimal thickening compared to that of normolipidemia. In cases of poor distal runoff, the enhancement of the intimal thickening by hypercholesterolemia is augmented. 3) 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. 4) HVJ-liposomes containing encapsulated bovine ecNOS cDNA or control vector plasmid was implanted into the autogenous vein grafts under hypercholesterolemic rabbits. 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.