| Project/Area Number |
16390089
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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 |
Pathological medical chemistry
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| Research Institution | University of Yamanashi (2006)
University of Tsukuba (2004-2005) |
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Principal Investigator |
FAN Jianglin University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Professor, 医学工学総合研究部, 教授 (60272192)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Fumihiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院人間総合科学研究所, 助教授 (90226481)
YAMADA Nobuhiro University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院人間総合科学研究所, 教授 (40200729)
WATANABE Teruo Saga University, Honorary Professor, 名誉教授 (40037396)
MORIMOTO Masatoshi Saga University, Analytic Research Center of Experimental Sciences, Associate Professor, 総合分析実験センター・生物資源開発部門, 助教授 (90136482)
孫 慧君 筑波大学, 大学院・人間総合科学研究科, 助手 (00361329)
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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 |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | Transgenic rabbits / CRP / Atherosclerosis / Hypercholesterolemia / Macrophages / Plaque / Animal model / Inflammation / C-反応蛋白 / 遺伝子改変 / 動物モデル / 脂質代謝 / 遺伝子導入 / CRP |
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| Research Abstract |
In this project, we have performed two studies in order to elucidate the functional roles of CRP in atherosclerosis. In the initial study, we used both human and rabbit specimens in attempt to clarify (1) whether CRP is present in the lesions, (2) if so, where CRP is deposited, (3) whether vascular cells especially macrophages can synthesize CRP. Our study showed that CRP is ubiquitously present in the lesions regardless of the lesion stage. CRP is closely associated with apoB but not macrophages. Using both Northern blotting and real-time RT-PCR, we demonstrated that CRP mRNA is basically expressed in the liver but rarely, if any, by macrophages. We also demonstrated that in hypercholesterolemic rabbits, the aortic lesion size is positively correlated with the levels of plasma CRP. In order to demonstrate whether CRP is directly involved in the lesion formation, we also generate transgenic rabbits expressing human CRP in the liver. For this study, we used a liver-specific expression construct along with insulators and established three independent lines of CRP transgenic rabbits. Now, we are using these CRP transgenic rabbits to perform atherosclerosis study. We also obtained CRP inhibitors from ISIS company and hope to investigate whether inhibition of CRP can prevent atherosclerosis.
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