Intraoperative transfection of vein grafts with the NFkappaB decoy in a canine aortocoronary bypass model: a strategy to attenuate intimal hyperplasia.

ABSTRACT

BACKGROUND: The nuclear transcriptional factor NFkappaB is reported to play an important role in the expression of genes for neutrophil and macrophage chemotactic factors, adhesion molecules, and cell cycle-regulating proteins. In aortocoronary bypass surgery, the saphenous vein often develops vein graft disease. Here, we investigated whether transfection of a cis element decoy oligodeoxynucleotide of NFkappaB (NFkappaB decoy) into the vein graft wall suppresses neointimal hyperplasia and the differentiation of medial smooth muscle cells. METHODS: We established a canine aortocoronary bypass grafting model that has a saphenous vein graft between the left anterior descending coronary artery and the descending aorta. Pressure-mediated transfection of a scrambled (SD group; n = 5) or NFkappaB decoy (ND group; n = 5) into the graft wall was performed intraoperatively. The grafts were gently harvested at 4 weeks postoperative, and the middle portion of the graft was examined histopathologically. RESULTS: The average neointimal area of the ND group was significantly suppressed (SD group, 2.63 +/- 1.00 mm2 vs ND group, 0.88 +/- 0.66, p < 0.05), and the differentiation and proliferation of the medial smooth muscle cells in the ND group were also suppressed (proliferating cell nuclear antigen index SD group, 56 +/- 24 vs ND, 13 +/- 4, p < 0.05). CONCLUSIONS: These results demonstrated the efficacy of intraoperative transfection of the NFkappaB decoy into the vein graft wall for attenuation of neointima formation.