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THE JOURNAL OF CARDIOVASCULAR SURGERY
Rivista di Chirurgia Cardiaca, Vascolare e Toracica
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
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ORIGINAL ARTICLES VASCULAR SECTION
The Journal of Cardiovascular Surgery 2007 August;48(4):463-70
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
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.