| Project/Area Number |
16590328
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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 |
Experimental pathology
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| Research Institution | University of the Ryukyus (2006-2007)
Kurume University (2004-2005) |
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Principal Investigator |
KATO Seiya University of the Ryukyus, Medicine, Professor (60268844)
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| Co-Investigator(Kenkyū-buntansha) |
HOSHINO Tomoaki Kurume University, Medicine, Lecturer (00261066)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | atherosclerosis / inflammation / Th1 response / cytokine / interleukin-4 (IL-4) / mouse / cell culture / Thl反応 |
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| Research Abstract |
Inflammatory process of atherosclerosis and its therapeutic implication have been studied. LPA (Lysophosphatidic acid) showed mitogenic activity in the cultured smooth muscle cells as well as induction of NADPH-dependent intracellular oxidative stress, rac-1 (small GTPase) activation, and MCP-1 expression, of which pathway was inhibited by antioxidant and statin. Such in vitro experiments suggested an inflammatory phenotype of vascular cells. Administration of soluble INF_<-γ> receptor in ApoE knockout mice resulted in the suppression of atherogenesis. Moreover, STAT6 knockout mice (B6 backbone) showed not only Th1 shift in the immunological response but the phenotypes of obesity and glucose tolerance, suggesting a close relationship between inflammatory, immunological process and atherosclerosis or metabolic risk factors. Wild type mouse IL-4 gene and its specific cell oriented mutein, Q116E, were sub-cloned into adenovirus-derive expression (shuttle) vector. Primary mouse vascular cells were tested for the changes in inflammatory phenotypes. Development of replication-deficient adenoviral vector was attempting for in vivo experiments. These results further highlighted the importance of inflammatory process of atherosclerosis and suggest the therapeutic implications. We gratefully appreciate for supporting our work and continue to make our best effort to dissolve the pathological problems in human cardiovascular diseases.
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