| Project/Area Number |
14570641
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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 | The University of Tokyo |
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Principal Investigator |
ANDO Katsuyuki The University of Tokyo, Health Service Center, Lecturer, 保健管理センター, 講師 (60184313)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Katsutoshi The University of Tokyo, Faculty of Medicine, Assistant, 大学院・医学系研究科, 助手 (00292863)
下沢 達雄 東京大学, 大学院・医学系研究科, 助手 (90231365)
FUJITA Toshiro The University of Tokyo, Faculty of Medicine, Professor, 大学院・医学系研究科, 教授 (10114125)
ISSHIKI Masashi The University of Tokyo, Faculty of Medicine, Assistant, 大学院・医学系研究科, 助手 (70302734)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | lectin-like oxidized LDL receptor-1 (LOX-1) / cytokine / thiazolidinediones / peroxisome proliferator-activated receptor-γ (PPARγ) / atherosclerosis / lpr mice / PPARγ knockout mice / tumor necrosis factor-α (TNFα) / lprマウス / TNAα / LOX-1 / PPARγ / 腎障害 / 酸化ストレス / タウリン |
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| Research Abstract |
The purpose of this project is to clarify the possible relationship of peroxisome proliferator-activated receptor-γ(PPARγ), which is proposed to inhibit the development and progression of atherosclerosis, and lectin-like oxidized low density lipoprotein (LDL) receptor-i1 (LOX-1), which is considered to play an important role in vascular damage. We demonstrated that PPARγ ligands suppressed LOX-1 overexpression induced by cytokine in bovine aortic endothelial cells (BAEC). Moreover, we elucidated that cytokine (tumor necrosis factor-α TNFα) enaqhnced LOX-1 expression in kidney and aorta of C57/BL6 mice, which was inhibited by thiazolidinediones, a PPARγ ligand. That is, the in-vitro finding was also observed in in-vivo experiment. Then, we evaluated whether LOX-1 expression is upregulated in lpr mice, in which the expression of TNFα is enhanced, as compred to normal mice. However, renal LOX-1 expression was not elevated in lpr mice. The LOX-1 expression might be modified by several autoimmune abnormality. In addition, we used PPARγ knockout heterozygote mice (homozygote mice are viviparously lethal). However, TNFo-induced renal LOX-1 upregulation was not different between PPARγ knockout mice and wild-tupe mice and effect of PPARγ ligand also did not differ. Thus, our results explain pharmacological mechanism of the antiatheroeclerotic action of thiazolidinediones, but do not suggest a role of intrinsic PPARγ, although our data have limitation because the konckout mice were heterozygote.
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