| Project/Area Number |
13671241
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nagoya University (2002)
Kyushu University (2001) |
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Principal Investigator |
KOMORI Kimihiro Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40225587)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Masahiro Nagoya University, Graduate School of Medicine, Associate professor, 大学院・医学系研究科, 助教授 (70273240)
KOBAYASHI Masayoshi Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (60329381)
NISHIKIMI Naomichi Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (40242862)
YONEMITSU Yoshikazu Kyushu University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (40315065)
古山 正 九州大学, 医学部・附属病院, 医員(臨床)
庄司 哲也 九州大学, 医学部・附属病院, 医員(臨床)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | intimal thickening / MCP-1 / gene therapy / late graft failure / 血管内膜肥厚 |
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| Research Abstract |
Although grafting with an autologous vein as a vascular substitute in the treatment of peripheral arterial occlusive disease is the surgical procedure that yields the best long-term results, late vein graft failure remains a significant problem for vascular surgeons. Infiltration and activation of monocytes in, the arterial wall mediated by monocyte chemoattractant protein-1 (MCP-1) might be a major cause of restenosis after angioplasty. However, there is no direct evidence to support a definite role of MCP-1 in the development of restenosis.
We recently devised a new strategy for anti-MCP-1 gene therapy by transfecting an N-terminal deletion. mutant of the MCP-1 gene into skeletal muscles.
We found that after balloon injury, the MCP-1 mRNA level significantly increased as early as day 1, but declined with time ; at all points in time, however, gene expression of MCP-1 in the injured artery was significantly higher on days 3, 7, and 28 than that in the noninjured control artery. Appearance of RAM11-positive macrophages were not distinct on day 1, but became evident on days 3, 7, and 28. We found that 7ND gene transfer markedly suppressed macrophage infiltration into the intima, media, and adventitia after balloon injury.
We found that intimal area and intima/media ratio were less in 7ND group than in PBS or empty plasmid group and that negative remodeling (smaller lumen size, IEL and EEL) was less in 7ND group than in PBS or empty plasmid group. As a result of the inhibition of neointimal formation and negative remodeling, luminal narrowing was prevented.
MCP-1-mediated monocyte infiltration is necessary in the development of restenotic changes to balloon injury in hypercholesterolemic rabbits. This strategy may be a useful and practical form of gene therapy against human restenosis.
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