Pharmacotherapy for abdominal aortic aneurysm by the inhibition of c=jun N-terminal kinase
| Project/Area Number |
16390365
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Yamaguchi University |
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Principal Investigator |
AOKI Hiroki Yamaguchi University, School of Medicine, Associate Professor, 医学部, 助教授 (60322244)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Koichi Yamaguchi University, School of Medicine, Research Associate, 医学部, 助手 (00322248)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2006: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2005: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | aortic aneurysm / atheroscleosis / c-Jun N-terminal kinase / JNK / animal model / therapy / JNK inhibitor / regression |
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| Research Abstract |
Abdominal aortic aneurysm is a common disease among elderly people that, when surgical treatment is inapplicable, results in progressive expansion and rupture of the aorta with high mortality. Although non-surgical treatment for aortic aneurysm is much awaited, few opt ions are available because its molecular pathogenesis remains elusive. We identified JNK as a proximal signaling molecule in the pathogenesis of aortic aneurysm. Human abdominal aortic aneurysm tissue showed high level of phospho-JNK. We show that JNK programs a gene expression pattern in different cell types, which cooperatively enhances the degradation of the extracellular matrix, while suppressing biosynthetic enzymes of the extracellular matrix. Selective JNK inhibition in vivo not only prevented the development of aortic aneurysm but also caused regression of established aortic aneurysm in two mouse models. Therefore, JNK promotes abnormal extracellular matrix metabolism in the tissue of aortic aneurysm and may represent a novel therapeutic target.
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Report
(4 results)
Research Products
(39 results)
