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

Abstract

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. 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. 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). These results demonstrated the efficacy of intraoperative transfection of the NFkappaB decoy into the vein graft wall for attenuation of neointima formation.