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Activation of Arterial Wall Cells during Atherogenesis : A study using a in vitor co-culture model system

Research Project

Project/Area Number 15209026
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

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)

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)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
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)
KeywordsATHEORSCLEROSIS / 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
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.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (19 results)

All 2005 2004 2003 Other

All Journal Article (15 results) Publications (4 results)

  • [Journal Article] The isolation of mouse aortic endothelial cells by a simple method.2005

    • Author(s)
      Kobayashi M, Inoue K, Warabi E, Minami T, Kodama T
    • Journal Title

      J Atheroscler Thromb (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Expression of the LXR{alpha} Protein in Human Atherosclerotic Lesions.2005

    • Author(s)
      Watanabe Y, Jiang S, Takabe W, Ohashi R, Tanaka T, Uchiyama Y, Katsumi K, Iwanari H, Noguchi N, Naito M, Hamakubo T, Kodama T.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 25(3)

      Pages: 622-627

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of the LXR{alpha} Protein in Human Atherosclerotic Lesions.2005

    • Author(s)
      Watanabe Y, Jiang S, Takabe W, Ohashi R, Tanaka T, Uchiyama Y, Katsumi K, Iwanari H, Noguchi N, Naito M, Hamakubo T, Kodama T.
    • Journal Title

      Arterioscler Thromb Vase Biol 25(3)

      Pages: 622-627

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of the LXR{alpha} Protein in Human Atherosclerotic Lesions.2005

    • Author(s)
      Watanabe Y., Jiang S, Takabe W, Ohashi R, Tanaka T, Uchiyama Y, Katsumi K, Iwanari H, Noguchi N, Naito M, Hamakubo T, Kodama T.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 25(3)

      Pages: 622-627

    • Related Report
      2004 Annual Research Report
  • [Journal Article] VEGF- and thrombin-induced termination factor, down syndrome critical region-1,attenuates endothelial cell proliferation, and angiogenesis.2004

    • Author(s)
      Minami T, Horiuchi K, Miura M, Abid R, Takabe W, Kohro T, Ge X, Aburatani H, Hamakubo T, Kodama T, Aird WC.
    • Journal Title

      J Biol Chem. 279(48)

      Pages: 50537-50554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect on endothelial cell gene expression of shear stress, oxygen concentration, and low-density lipoprotein as studied by a novel flow cell culture system.2004

    • Author(s)
      Warabi E, Wada Y, Kajiwara H, Kobayashi M, Koshiba N, Hisada T, Shibata M, Ando J, Tsuchiya M, Kodama T, Noguchi N.
    • Journal Title

      Free Radic Biol Med. 1;37(5)

      Pages: 682-694

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interaction between Hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated VEGF signaling.2004

    • Author(s)
      Minami T, Murakami T, Horiuchi K, Miura M, Noguchi T, Miyazaki JI, Hamakubo T, Aird WC, Kodama T.
    • Journal Title

      J Biol Chem. 279(20)

      Pages: 20626-20635

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] VEGF-and thrombin-induced termination factor, down syndrome critical region-1, attenuates endothelial cell proliferation, and angiogenesis.2004

    • Author(s)
      Minami T, Horiuchi K, Miura M, Abid R, Takabe W, Kohro T, Ge X, Aburatani H, Hamakubo T, Kodama T, Aird WC.
    • Journal Title

      J Biol Chem. Nov 26;279(48)

      Pages: 50537-542001

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect on endothelial cell gene expression of shear stress, oxygen concentration, and low-density lipoprotein as studied by a novel flow cell culture system2004

    • Author(s)
      Warabi E, Wada Y, Kajiwara H, Kobayashi M, Koshiba N, Hisada T, Shibata M, Ando J, Tsuchiya M, Kodama T, Noguchi N.
    • Journal Title

      Free Radic Biol Med. Sep 1;37(5)

      Pages: 682-694

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] VEGF-and thrombin-induced termination factor, down syndrome critical region-1, attenuates endothelial cell proliferation, and angiogenesis.2004

    • Author(s)
      Minami T, Horiuchi K, Miura M, Abid R, Takabe W, Kohro T, Ge X, Aburatani H, Hamakubo T, Kodama T, Aird WC.
    • Journal Title

      J Biol Chem. Sep 23 ([Epubahesd of print])

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effect on cell gene expression by shear stress, oxygen concentration, low-density lipoprotein as studied by a novel flow cell culture system.2004

    • Author(s)
      Warabi E, Wada Y, Kajiwara H, Kobayashi M, Koshiba N, Hisada T, Shibata M, Ando J, Tsuchiya M, Kodama T, Noguchi N.
    • Journal Title

      Free Radic Biol Med. 1;37(5)

      Pages: 682-692

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interaction between Hex and GATA transcription factors in vascular endothelial cells Inhibits flk-1/KDR-mediated VEGF signaling.2004

    • Author(s)
      Minami T, Murakami T, Horiuchi K, Miura M, Noguchi T, Miyazaki JI, Hamakubo T, Aird WC, Kodama T.
    • Journal Title

      J Biol Chem. 279(20)

      Pages: 20626-20635

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thrombin stimulation of VCAM-1 in endothelial cells is mediated by PKC-delta -NF-kappa B and PKC-zeta -GATA signaling pathways.2003

    • Author(s)
      Minami T, Abid MR, Zhang J, King G, Kodama T, _Aird WO.
    • Journal Title

      J Biol Chem. 278

      Pages: 6976-6984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Thrombin stimulation of VCAM-1 in endothelial cells is mediated by PKC-delta -NF-kappa B and PKC-zeta -GATA signaling pathways.2003

    • Author(s)
      Minami T, Abid MR, Zhang J, King G, Kodama T, Aird WC.
    • Journal Title

      J Biol Chem. 278(9)

      Pages: 6976-6984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Thrombin stimulation of VCAM-1 in endothelial cells is mediated by PKC-delta -NF-kappa B and PKC-zeta -GATA signaling pathways.2003

    • Author(s)
      Minami T, Abid MR, Zhang J, King G, Kodama T, Aird WC.
    • Journal Title

      J Biol Chem. 278

      Pages: 6976-6984

    • Related Report
      2004 Annual Research Report
  • [Publications] T.Minami, T.Kodama, et al.: "Thrombin and Phenotype Modulation of the Endothelium."Arterioscler.Thromb.Vasc.Biol.. 24. 41-53 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Minami, T.Kodama, et al.: "Ets Motifs are Necessary for Endothelial Cell Specific Expression of a 723-bp Tie-2 Promoter/Enhancer in Hprt-Targeted Transgenic Mice."Arterioscler.Thromb.Vasc.Biol.. 23. 2041-2043 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] N.Noguchi, R.Hanyu, A.Nonaka, Y.Okimoto, T.Kodama: "Inhibition of THP-1 cell adhesion to endothelial cells by α-tocopherol and α-tocotrienol is dependent on intracellular concentration of the antioxidants."Free Rad.Biol.Med. 34. 1614-1620 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Y.Okimoto, E.Warabi, Y.Wada, E.Niki, T.Kodama, N.Noguchi: "A novel method of following oxidation of low-density lipoprotein using a sensitive fluorescent probe, diphenyl-1-pyrenylphosphine."Free Rad.Biol Med.. 5. 576-585 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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