| Project/Area Number |
15209026
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KODAMA Tatsuhiko The University of Tokyo, Research Center for Advanced Science and Technology, Professor, 先端科学技術研究センター・任期付特別教員(教授) (90170266)
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| Co-Investigator(Kenkyū-buntansha) |
NAITO Makoto Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (30045786)
DOI Takefumi Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00211409)
NOGUCHI Noriko The University of Tokyo, Research Center for Advanced Science and Technology, Associate Professor, 先端科学技術研究センター, 科学技術振興特任教員(特任助教授) (40198578)
MINAMI Takashi The University of Tokyo, Research Center for Advanced Science and Technology, Associate Professor, 先端科学技術研究センター, 科学技術振興特任教員(特任助教授) (00345141)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥49,270,000 (Direct Cost: ¥37,900,000、Indirect Cost: ¥11,370,000)
Fiscal Year 2004: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2003: ¥33,670,000 (Direct Cost: ¥25,900,000、Indirect Cost: ¥7,770,000)
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| Keywords | ATHEORSCLEROSIS / ENDOTHELIAL CELL / ADHESION MOLECULE / TRANSCRIPTINAL FACTORS / NFATC / DSCR1 / NRF2 / GATA / Rac1 / コレステロール / ラフト / 炎症 / マイクロアレイ / 血管内皮細胞 / トロンビン / TNF-a / target transgenic mouse / Tie-2 |
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| Research Abstract |
<Purpose>A new in vitro system for the co-culture of vascular endothelial cell(EC), smooth muscle cell(SMC) and monocyte/macrophage has been developed for the anaylysis of pathogenesis of atherosclerosis.
<Method>We have established a vascular cell under flow. Using this system we examined the molecular pathogenesis of atherosclerosis and endothelial activation.
Results
(1)Oxidative modification of lipoproteins : We established a method for tracing oxidative modification. Transcriptome analysis indicated lyso-PC affects many genes in EC.
(2)Using co-culture system, we found the involvement of NRF2 in shear stress sensing.
(3)Changes in transcriptome were analyzed during inflammation, growth and coagulation in EC. Adding to Ets, GATA and Hex, the role of NFATc in these signal transduction was found. We also found that DSCRl can inhibit NFATc signaling.
(4)We found a novel inhibitor for upregulation of adhesion molecule using co-culture system. This drug is also effective for the treatment of psoriasis.
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