1998 Fiscal Year Final Research Report Summary
Development of therapeutic methods for arterial restenosis : intraarterial radiation, pharmaceutical approach and gene therapy
| 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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| Keywords | BTEB2 / smooth muscle cells / phenotypic modulation / transcription factor / klotho / intracoronary radiation / radioactive stent / ^<113>Xe |
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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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[Publications] Watanabe S,Osa A,Sekine T,Ishioka N,Koizumi M,Kojima T,Hasegawa A,Yoshii M,Okamoto E,Aoyagi K,Miyajima A, Nagai R.: "Production of a radioactive endovascular stent by implantation of ^<113>Xe ions." Applied Radiation and Isotopes. in press.
Description
「研究成果報告書概要(欧文)」より
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[Publications] Watanabe N,Kurabayashi M,Shimomura Y,Hoshino Y,Manabe I,Watanabe M,Aikawa M,Kuro-o M,Suzuki T,Yazaki Y,Nagai R: "BTEB2, a Kruppel-Like Transcription Factor, Regulates Expression of the SMemb/Non-Muscle Myosin Heavy ChainB(SMemb/NMHC-B)Gene" submitted.
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「研究成果報告書概要(欧文)」より
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[Publications] Kuro-o M,Matsumura Y,Aizawa H,Kawaguchi H,Suga T,Utsugi T,Ohyama Y,Kurabayashi M,Kaname T,Kume E,Iwasaki H,Iida A,Shiraki-Iida T,Nishikawa S,Nagai R,Nabeshima Y.: "Mutation of the mouse Klotho gene leads to a syndrome resembling ageing." Nature. 390(6655). 45-51 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Saito Y,Yamagishi T,Nakamura T,Ohyama Y,Aizawa H,Suga T,Matsumura Y,Masuda H,Kurabayashi M,Kuro-o M,Nabeshima Y,Nagai R.: "Klotho protein protects against endothelial dysfunction." Biochem Biophys Res Commun. 248(2). 324-329 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Aizawa H,Saito Y,Nakamura T,Inoue M,Imanari T,Ohyama Y,Matsumura Y,Masuda H,Oba S,Mise N,Kimura K,Hasegawa A,Kurabayashi M,Kuro-o M,Nabeshima Y,Nagai R.: "Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats." Biochem Biophys Res Commun. 249(3). 865-871 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohyama Y,Kurabayashi M,Masuda H,Nakamura T,Aihara Y,Kaname T,Suga T,Arai M,Aizawa H,Matsumura Y,Kuro-o M,Nabeshima Y,Nagai R: "Molecular cloning of rat klotho cDNA : markedly decreased expression of klotho by acute inflammatory stress." Biochem Biophys Res Comm. 251(3). 920-925 (1998)
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「研究成果報告書概要(欧文)」より
