| Project/Area Number |
07044255
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KITA Toru Graduate School of Medicine, Kyoto University, Professor, 医学研究科, 教授 (60161460)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Kenji Graduate School of Medicine, Kyoto University, Instructor, 医学研究科, 助手 (00212811)
CYBULSKI Myr ハーバード大学, 医学部, 講師
CHAIT Alan University of Washington, Professor, 医学部, 教授
GIMBRONE Jr ハーバード大学, 医学部, 教授
OCHI Hiroshi Graduate School of Medicine, Kyoto University, Instructor, 医学研究科, 助手 (80204220)
KUME Noriaki Graduate School of Medicine, Kyoto University, Instructor, 医学研究科, 助手 (20252455)
WAKATSUKI Yoshio Graduate School of Medicine, Kyoto University, Lecturer, 医学研究科, 講師 (40220826)
YOKODE Masayuki Graduate School of Medicine, Kyoto University, Lecturer, 医学研究科, 講師 (20252447)
CYBULSKY Myron I Harvard Medical School, Assistant Professor
GIMBRONE Michael A.Jr Harvard Medical School, Professor
CYBULSKY Myr ハーバード大学, 医学部, 講師
GIMBRONE Mic ハーバード大学, 医学部, 教授
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1996: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1995: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Oxidized LDL / WHHL-rabbit / Lysophosphatidyl-choline / T-lymphocytes / Adhesion molecule / Smooth muscle growth factor / Atherosclerosis / Macrophages / INF-gamma / P selectin / HB‐EGF / PDGF / INF‐γ / IL‐2受容体 |
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| Research Abstract |
We are focussing on the atherogenesity of oxidized LDL,in particular lysophosphatidyl-choline (Lyso-PC) which generated in atherosclerotic lesions. Lyso-PC has been shown to differentially up regulate adhesion molecules, such as VCAM-1 and ICAM-1 expression and growth factors in various cultured cells, including endothelial cells, macrophages and T cells. In addition, INF-gamma and IL-2 receptor are induced by Lyso-PC in T cells.
In case of PDGF-B chain and ICAM-1, induction of these molecules are independent of PMA-regulatable PKC activation but suppressed by increased level of intracellular cyclic AMP in cultured endothelial cells. In addition, induction of PDGF-B chain is required newly synthesized protein, probably transcriptional factor. Therefore we put forward on the signal transduction system of Lyso-PC,concerning the expression of ICAM-1 and PDGF-B chain collaboration with both Dr.Chait, Cybulsky and Gimbrone.
We also investigated the sequential expression of P-selectin, VCAM-1, E-selectin, activated macrophages and T lymphocytes in and on the endothelial cellsby antibodies respectively, using cholesterol fed rabbits at the orifice of first branch of intercostal artery. At one week of cholesterol feeding, P-selectin and VCAM-1 are detected. And activated macrophages are observed in the same place at following 2 weeks. At three week after cholesterol-feeding, T-lymphocytes are detected at the same place and continued to be detected until 10 weeks. However E-selectin was not detected.
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