Role of p38 MAP kinase in intimal hyperplasia of vein graft

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Asahikawa Medical College
• Principal Investigator: AKASAKA Nobuyuki Asahikawa Medical College, School of Medicine, Assistant Professor, 医学部, 助手 (30281885)
• Co-Investigator(Kenkyū-buntansha): INABA Masashi Asahikawa Medical College, School of Medicine, Associate Professor, 医学部, 助教授 (70151587) ; UCHIDA Hisashi Asahikawa Medical College, School of Medicine, Assistant Professor, 医学部, 助手 (60301991) ; 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)
• Project Period (FY): 2002 – 2003
• Keywords: vein graft / intimal hyperplasia / graft stenosis / decoy / Nuclear Factor Kappa B (NFkB) / p38 / MAP kinase / NFkB decoy

Research Abstract

Intimal hyperplasia of vein grafts is still unsolved problem. We focused on stess-responsed protein such as p38 MAP kinase and NFkB as major causes of vein graft remodeling. We performed in-vivo experiments of canine saphenous vein grafting which replaced their femoral arteries, and evaluated morphological analysis and western blotting of proteins extracted from vein graft. The results are as follows ;
1)p38 activation m vein grafting model : p38 activation was evaluated by western blotting of vein grafts with phospho-p38 antibody. However, no remarkable activation was found m any vein grafts harvested at 30min, 2hours, 2days, and 7days after grafting.
2)NFkB activation in vein graft model : Western blotting of phospho-IkB of vein grafts indicated that phospho-IkB markedly increased at 2hours after grafting, and the phosphorylation lasted until 7days after grafting. This result is the first evidence showing activation of NFkB in vein grafts.
3)Role of NFkB activation in the intimal hyperplasia of vein grafts : To evaluated the role of NFkB activation, NFkB decoy was transferred by use of HVJ-Envelope vector ex-vivo before vein grafting(NFkB decoy group). As control, scramble decoy was administrated in the vein grafts(scramble decoy group). One month after grafting, severe intimal hyperplasia of vein grafts were found in scramble decoy group, while the intimal hyperplasia of vein grafts were significantly suppressed compared to that of scramble decoy group(p<0.05). These results suggested that NFkB activation immediately after bypass grafting played important role in intimal hyperplasia of vein grafts.
In conclusions, the activation of NFkB is key reaction of vein graft remodeling, and suppress of NFkB activation can be attractive treatment to prevent vein graft stenosis due to intimal hyperplasia.