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THE JOURNAL OF CARDIOVASCULAR SURGERY

A Journal on Cardiac, Vascular and Thoracic Surgery


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The Journal of Cardiovascular Surgery 2007 August;48(4):463-70

language: English

Effect on vein graft intimal hyperplasia of nuclear factor-kB decoy transfection using the second generation of HVJ vector

Shimizu N. 1, Azuma N. 1, Nishikawa T. 2, Hirata S. 1, Morishita R. 3, Kaneda Y. 2, Sasajima T. 1

1 Department of Surgery, Asahikawa Medical University Asahikawa, Hokkaido, Japan
2 Division of Gene Therapy Science Graduate School of Medicine, Osaka University Suita, Osaka, Japan
3 Division of Clinical Gene Therapy Graduate School of Medicine, Osaka University Suita, Osaka, Japan


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Aim. Vein graft stenosis due to intimal hyperplasia (IH) is the main cause of graft failure. We examined possibilities of nuclear factor-kB (NF-kB) expression in vein grafts, and inhibitive effects of NF-kB decoy on the gene expression and subsequent vein graft IH.
Methods. Fifteen mongrel dogs underwent femoral artery replacement with autogenous vein grafts. Group I: grafts were retrieved at a predetermined time and subjected to NF-kB binding activity assay; Groups II and III: grafts were transfected with scrambled (II-a, III-a) or NF-kB (II-b, III-b) decoy using hemagglutinating virus of Japan envelope before implantation. Grafts were retrieved 7 days after implantation for evaluation of intercellular adhesion molecule-1 (ICAM-1) mRNA expression (Group II) and 4 weeks after implantation for comparison of IH by morphometric analysis (Group III).
Results. NF-kB binding activity was increased in a time-dependent manner, with a peak 2 days after implantation. The ratio between ICAM-1 and glyceraldehyde-3-phosphate dehydrogenase mRNA expression in II-b was significantly lower than that in II-a (0.347 ± 0.07 versus 0.612±0.08; P = 0.047). The ratio of intimal cross-section area to luminal cross-section area of III-b was significantly lower than that of the III-a (0.096±0.03 versus 0.461±0.11; P = 0.048).
Conclusion. NF-kB binding activity in vein grafts increases after implantation, and transfection of NF-kB decoy before implantation may reduce IH through the inhibition of ICAM-1 expression.

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