| Project/Area Number |
16590655
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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 |
Circulatory organs internal medicine
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
HASEBE Naoyuki Asahikawa Medical College, Faculty of medicine, Associate Professor, 医学部, 助教授 (30192272)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Redox system / base excision repair / vascular remodeling / atherosclerosis / angiotensin II / oxidative stress / glutathione / Ape1 / 熱ショックタンパク / NADPH oxydase / MCP-1 / angiotensin II / 塩基除去修復機構 |
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| Research Abstract |
Alteration of angiotensin II-induced vascular remodeling was investigated in impaired reduced glutathione (GSH) redox system in cuff-induced vascular injury mode. The impaired GSH redox status was set by buthionine sulfoximine (BSO) treatment, which did not affect hemodynamics by itself. Superoxide production in vascular wall was markedly enhanced in angiotensin II+BSO, however, the vascular remodeling.induced by angiotensin II was totally abolished in the impaired redox system. We have elucidated that the mechanism was actuated via enhancement of apoptosis in the neointima and suppression of cell growth in the media. Meanwhile, we have confirmed the enhanced expression of Ape1 gene in the wire-injured arteries of mice, particularly in the neointimal lesion. We have produced AP1 gene inserted plasmid and trasnfected to adenovirus. The role of AP1 gene as a key player of base excision repair (BER) system in atherosclerosis process was investigated in the H2O2-induced oxidative damage in cultured vascular smooth muscle cells. The interaction of BER system and antiatherosclerotic mechanism has been investigated in in vivo model, and has been proposed as the new target for atherosclerosis threatment.
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