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Ann Thorac Surg 2002;74:1132-1137
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

Intraoperative transfection of vein grafts with the NF{kappa}B decoy in a canine aortocoronary bypass model: a strategy to attenuate intimal hyperplasia

Takuji Shintani, MDa, Yoshiki Sawa, MDa, Toshiki Takahashi, MDa, Goro Matsumiya, MDa, Nariaki Matsuura, MDb, Yuji Miyamoto, MDa, Hikaru Matsuda, MDa*

a Department of Surgery, Course of Interventional Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
b Department of Pathology, School of Allied Sciences, Faculty of Medicine, Osaka University, Osaka, Japan

Accepted for publication June 17, 2002.

* Address reprint requests to Dr Matsuda, Department of Surgery, Course of Interventional Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
e-mail: matsuda{at}surg1.med.osaka-u.ac.jp

BACKGROUND: The nuclear transcriptional factor NF{kappa}B 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 NF{kappa}B (NF{kappa}B 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 NF{kappa}B 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 NF{kappa}B decoy into the vein graft wall for attenuation of neointima formation.




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