Recombinant endothelial nitric oxide synthase gene transfer inhibits vein grafts neointima formation

Objective To evaluate nitric oxide augmentation in venous tissue by adenoviral-mediated gene transfer of endothelial nitric oxide synthase (Ad5CMVNOSⅢ) to reduce vein grafts restenosis. Methods Twenty-one canine were divided into three groups: operation control group, Ad5CMVLac-Z control group, and Ad5CMVNOSⅢ group. During operation of canine jugular vein into carotid artery interposition grafting, harvested canine jugular vein segments were exposed for 30min at 37℃ to either recombinant replication deficient adenovirus encoding eNOS(Ad5CMVNOSⅢ, 4.08× 10 10 pfu/ml), or control recombinant replication deficient adenovirus encoding E. coli β-galactosidase (Ad5CMVLac-Z, 2×10 10 pfu/ml). Quantitative histological studies of the vein segments were performed 28 days after operation. Results The average intimal-to-medial (I/M) ratio was calculated for each group one month after bypass operation. Compared to I/M ratio of normal canine jugular vein, the I/M ratio of operation control group veins, Ad5CMVLac-Z control group veins and Ad5CMVNOSⅢ group veins all increased significantly ( P 0.05). However, the I/M ratio of Ad5CMVNOSⅢ group vein grafts increased significantly less ( P 0.05). Conclusion Ad5CMVNOSⅢ gene therapy may reduce intimal hyperplasia.