OBJECTIVETo study the duration of prourokinase gene expression in vein grafts and the role of the prourokinase gene in protecting vein grafts from neointimal hyperplasia.

METHODSFifty-four Wistar rats were used in this study. In each rat, the jugular vein was excised and distended for 30 minutes using a solution containing either Adv(5)-CMV (control group) or Adv(5)-CMV/Pro-UK (treatment group). Next, the jugular vein was reversed and interposed into the divided carotid artery of the same rat. On the 14th day after transfection, vein grafts of the control group were collected in order to perform a fibrinolysis test for prourokinase (Pro-UK) activity. On the 2nd, 7th, 14th, 28th, and 60th day, the vein grafts of the treatment group were likewise collected in order to detect prourokinase activity. On the 28th day, the vein grafts of both groups were explanted to evaluate the (3)H-TDR incorporation so that pathologic analysis could be performed.

RESULTSPro-UK activity could not be detected in the control group, while in the treatment group, the Pro-UK activity could be detected from the 2nd day onwards, peaking on the 7th day and declining from the 14th day, but yet persisting at a low level for a further month. The amount of (3)H-TDR incorporated in the control group was higher than that in the treatment group. Pathologic analysis demonstrated that vein grafts of both groups exhibited wall thickening, but that the degree of graft neointimal hyperplasia and reduction of the graft lumen was greater in the control group than that in the treatment group. The occlusion rate of grafts in the control group was 20%. All grafts in the treatment group were patent.

CONCLUSIONSPro-UK gene transfer before vein grafting in vitro results in a high level of gene expression in the vein graft from the 7th day to 14th day. And its gene expression in the vein graft could reduce neointimal hyperplasia in the vein graft.