| Project/Area Number |
13307034
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YOKODE Msayuki Kyoto University Graduate School of Medicine, Professor, 医学研究科, 教授 (60161460)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Hidenori Kyoto University Graduate School of Medicine, Professor, 医学研究科, 助手 (60232021)
KUME Noriaki Kyoto University Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20252455)
横出 正之 京都大学, 医学研究科, 教授 (20252447)
TANAKA Makoto Kyoto University Graduate School of Medicine, Instructor, 医学研究科, 助手 (00271007)
HORIUCHI Hisanori Kyoto University Graduate School of Medicine, Instructor, 医学研究科, 助手 (90291426)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥53,300,000 (Direct Cost: ¥41,000,000、Indirect Cost: ¥12,300,000)
Fiscal Year 2002: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
Fiscal Year 2001: ¥30,160,000 (Direct Cost: ¥23,200,000、Indirect Cost: ¥6,960,000)
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| Keywords | atherosclerosis / oxidized LDL / LOX-1 / SR-PSOX / MCP-1 / plate activation / Gsr6 / PDGF receptor / 粥状動脈硬化 / スカベンジャー受容体 / ケモカイン / 細胞接着 / 細胞遊走 / 血栓 / 血小板 |
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| Research Abstract |
Aterosclerosis is formed by accumulation of cholesterol which is eaten as oxidized LDL by macrophages the arterial wall migrated from blood stream and differentiated from monocycles. At the process, many biological responses are accompanied. At the final step of atheroscrelosis is occlusion of the artery by thrombus formation which is caused by endothelial cell disruption followed by activation of platelets. We had elucidated that macrophages have multiple forms of oxidized LDL receptors and that lysophatidylcholine which is a phospholipids remarkably increased in oxidized LDL induces expression of cell adhesion molecules and growth factors. In this research, we obtained following findings : (1) We identified novel oxidized receptors, LOX-1 and SR-PSOX and determined their localization in the atherosclerotic lesions. (2) We found a novel function of LOX-l as a migrating factor. (3) We found that LOX-1 is cleaved to be released in the blood stream and that the concentration in the serum is increased in acute coronary syndrome. (4) We directly demonstrated that protein kinase alpha as an essential factor in granule secretion and aggregation of activated platelets. (5) We found that small GTPase Rab27 plays a critical role in dense-core granule secretion in platelets. (6) We found that a growth factor, Gas6 plays an important role in experimental nephritis caused by diabetes and immune complex. (7) We found that a chemokine MCP-1 uses distinct signaling pathways for cell adhesion and migration. (8) We found that PDGFalpha receptor and beta receptor play distinct roles in atherosclerosis formation.
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