Inhibition of vein graft intimal hyperplasia by gene transfer
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Asahikawa Medical College|
AZUMA Nobuyoshi Asahikawa Medical College, School of Medicine, Associate Professor, 医学部, 講師 (30250559)
SASAJIMA Tadahiro Asahikawa Medical College, School of Medicine, Professor, 医学部, 教授 (20109515)
INABA Masashi Asahikawa Medical College, School of Medicine, Associate Professor, 医学部, 助教授 (70151587)
HAGA Masae Asahikawa Medical College, School of Medicine, Assistant Professor, 医学部, 助手 (80271766)
|Project Period (FY)
2003 – 2006
Completed(Fiscal Year 2006)
|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 2006 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 2005 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2004 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2003 : ¥1,100,000 (Direct Cost : ¥1,100,000)
|Keywords||vein graft / intimal hyperplasia / graft stenosis / decoy / Nuclear Factor kappa B (NFkB) / HVJ / ICAM-1 / 遺伝子治療 / HGF|
Intimal hyperplasia of vein grafts is still unsolved problem. We focused on signal transduction relating inflammation such as NFkB, as major causes of the intimal hyperplasia. We performed in-vivo experiments of canine saphenous vein grafting which replaced their femoral arteries, and evaluated whether NFkB played crucial role in the intimal hyperplasia, and whether the decoy ODN of NFkB can be therapeutic procedure for vein graft stenosis.
The results are as follows;
1) NFkB binding activity of vein graft cells was increased in a time-dependent manner with a peak 2 days after implantation.
2)NFkB decoy transfected by HVJ-envelope vector inhibited the NFkB binding activity of vein graft cells.
3)Intimal hyperplasia of vein graft was significantly inhibited by NFkB decoy at one month after implantation, compared with that of scramble decoy(the ratio of intimal cross-sectional area to luminal cross-sectional area; 0.096±0.03 vs 0.461±0.11,p=0.048.
4)ICAM-1 mRNA expression of vein graft was also significantly suppressed by NFkB decoy(0.347±0.07 vs 0.612±0.08,p=0.047)
In conclusion, NFkB activity of vein graft cells increases after implantation, and transfection of NFkB before implantation can reduce intimal hyperplasia of vein graft through the inhibition of ICAM-1 expression which is the down-stream protein of NFkB. Futher improvement of the gene transfer methods are needed for therapeutic application of NFkB decoy.
Research Products (3results)