| Project/Area Number |
08557046
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gunma University School of Medicine |
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Principal Investigator |
NAGAI Ryozo Gunma University School of Medicine, 2nd Dept of Int Med, Professor, 医学部, 教授 (60207975)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Masashi Gunma University School of Medicine, 2nd Dept of Int Med, Assistant, 医学部, 助手 (60270857)
NAKAMURA Tetsuya Gunma University School of Medicine, 2nd Dept of Int Med, Assistant Professor, 医学部, 講師 (10272238)
HASEGAWA Akira Gunma University School of Medicine, 2nd Dept of Int Med, Associate Professor, 医学部, 講師 (80156306)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1996: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | BTEB2 / smooth muscle cells / phenotypic modulation / transcription factor / klotho / intracoronary radiation / radioactive stent / ^<113>Xe / ステント / 内膜肥厚 / 再狭窄 / 血管内照射療法 / ガンマ線 / 192Ir / 新生内膜 / 転写因子 / 動脈硬化 / 冠動脈 / 血管内照射 |
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| Research Abstract |
The objective of this study was to develop multiple approaches to prevent arterial restenosis, that is low-dose radioactive stents emitting beta-particle, pharmaceutical methods and gene therapy. We first implanted 133-Xe ions into tubular slotted stainless steel stents with the isotope separator installed at the TIARA (Takasaki Ion Accelerators for Advanced Radiation Application) facility at the Japan Atomic Energy Research Institute. The stents produced had homogeneous distribution of radioactivity and activity levels of 1.60*0.81 muCi. The radioactive stents were effective in preventing neointimal formation. Twenty-eight days after implantation in rabbit aorta, neointimal area was significantly reduced when to medial area ratio in the beta -particle emitting stents compared with control stents (0.43 *0.15 in radioactive stents versus 0.61*0.18 in control stents, p=0.05). Development of beta-particle emitting in Japan is important in that these stents cannot be imported because of short half-lives.
Regarding factrors that cause smooth muscle phenotypic modulation, we have identified zinc finger protein BTEB2 as a transcription factor for nonmuscle myosin heavy chain (SMemb) gene. BTEB2 also activates a number of vascular disease-associated genes, such as tissue factor, PAL-1, Egr-1 gene. BTEB2 gene is regulated by Egr- 1, an early response gene, through MEK1. These results suggest that BTEB2 functions as a transcription factor for phenotypic modulation of vascular smooth muscle cells, By using BTEB2 as a molecular marker, we found that retinoic acid and probucol deactivate macrophages as well as smooth muscle cell.
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