Investigation on cellular and molecular mechanism of angiogenesis and vascular remodeling and their novel therapeutic target
| Project/Area Number |
16590202
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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 pharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
KIM-MITSUYAMA Shokei Kumamoto University, Graduate School of Medical Sciences, Department of Pharmacology and Molecular Therapeutics, Professor, 大学院・医学薬学研究部, 教授 (10195414)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | ASK1 / angiogenesis / vascular remodeling / VEGF / MCP-1 / inflammatory cell / oxidative stress / ischemia / 活性酸素 |
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| Research Abstract |
The role of apoptosis signal-regulated kinase 1 (ASK1), which is MAP kinase kinase kinase, was examined in ischemia-induced angiogenesis and vascular remodeling. In vivo and in vitro studies, using ASK1 deficient mice and recombinant adenovirus containing dominant negative ASK1, indicated that hindlimb ischemia in mice caused the activation of ASK1 by the increase in oxidative stress and the activated ASK1 stimulates the infiltration of inflammatory cells such as leukocytes, macrophages, and T lymphocytes and the expression of VGEF and MCP-1, leading to the enhancement of angiogenesis. Furthermore, the activation of p38 and JNK seems to be at least in part involved in the underlying mechanism of angiogenesis by ASK1. Matrigel plug assay also showed that angiotensinII-induced angiogenesis is also attributable to ASK1 activation. Cuff injury or balloon injury was performed to examine the contribution of ASK1 in vascular remodeling. In vivo or in vitro data indicated that ASK1 activation enhances vascular smooth muscle cell proliferation and the migration of vascular smooth muscle cell to the intima, by mediating p38 and JNK, while ASK1 in bone marrow cells play a minor role in vascular intimal thickening. From these data, it is proposed that ASK1 may be the potential therapeutic target for angiogenesis and vascular remodeling
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Report
(3 results)
Research Products
(68 results)
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[Journal Article] Involvement of apoptosis signal-regulating kinase-1 on angiotensin II-induced monocyte chemoattractant protein-1 expression.2004
Author(s)
Omura T, Yoshiyama M, Kim S, Matsumoto R, Nakamura Y, Izumi Y, Ichijo H, Sudo T, Akioka K, Iwao H, Takeuchi K, Yoshikawa J.
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Journal Title
Arterioscler Thromb Vasc Biol. 24
Pages: 270-275
Related Report
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[Book] 臨床心臓病学2006
Author(s)
光山 勝慶
Total Pages
706
Publisher
文光堂
Description
「研究成果報告書概要(和文)」より
Related Report
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[Book] 酸化ストレスナビゲーター2005
Author(s)
光山 勝慶
Total Pages
331
Publisher
メディカルレビュー社
Description
「研究成果報告書概要(和文)」より
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[Book] ARB の新しい展開2005
Author(s)
光山 勝慶
Total Pages
239
Publisher
日本医学出版
Description
「研究成果報告書概要(和文)」より
Related Report
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[Book] 心臓ナビゲーター2004
Author(s)
光山 勝慶
Total Pages
362
Publisher
メディカルレビュー社
Description
「研究成果報告書概要(和文)」より
Related Report
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