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

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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.