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The mechanisms of atheroma formation in vessel wall using a unique monoclonal antibody(ASH1a/256C) recognizing. atherosclerotic lesions.

Research Project

Project/Area Number 14572068
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTeikyo University

Principal Investigator

MORI Masahiro  Teikyo University, Fac. Pharm. Sci, Research Assoc., 薬学部, 助手 (00230079)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsatherosclerosis / foam cell / cholesterol / apoptosis / lipid droplets / modified LDL / monoclonal antibody / non-invasive diagnosis / マクロファージ / Cholesterol / Phosphatidylcholine / 非浸襲的診断
Research Abstract

In order to investigate application for low invasive diagnosis of cardiovascular disease, novel monoclonal antibodies (ASH1a/256C) recognizing fatty streaks of atheroma in vivo and in vitro were prepared. The ASH1a/256C antigen purified from WHHL rabbit (a model animal for familial hyper The expression of PC-cholesterol complex correlates foam cell rupture and accumulation of lipid in extracellular space in intima) atheroma was determined as "PC-cholesterol complex" specifically localized in extracellular space in thickened intima.
Foam cells can produce this antigen as "FC (free cholesterol) enriched lipid droplets", only when macrophages incubated with Acetylated LDL, WHHL rabbit serum or Human hyperlipidemic serum. VLDL/IDL could also induce foam cell formation, however, no FC-rich lipid droplets were observed. The foam cells containing FC-rich lipid droplets were cultured continuously until 2 weeks ; finally, the foam cells ruptured and lipid droplets remained in extracellular matrix.
When the macrophage incubated with cholesterol oleate liquid crystals (not contain PC), macrophages could also produce PC-cholesterol complex (FC-rich lipid droplets) and change to foam cells morphologically, Since U18666A inhibited cellular cholesterol transport, when the foam cell incubated continuously with this material, foam cells failed to rupture themselves. These observation suggest that hydrolysis of CE (cholesteryl ester) and cellular cholesterol transport are important process for the formation of FC-rich lipid droplets
The expression of PC-cholesterol complex correlates foam cell rupture and accumulation of lipid in extracellular space in intima

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Itabe, H., Mori M., Fujimoto, Y., Higashi, Y., Takano, T.: "Minimally modified LDL is an oxidized LDL enriched with oxidized phosphatidylcholine"J.Biochem(Tokyo). 134. 459-465 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higashi, Y., Itabe, H., Mori, M., Fujimoto, Y., Takano T.: "Transmembrane lipid transfer is crucial for providing neutral lipids during VLDL assembly in endoplasmic reticulum"J.Biol.Chem. 278. 21450-21458 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujimoto, Y., Itabe, H., Mori, M., Higashi, Y., Kojima, S., Takano, T.: "Identification of the major lipid droplet proteins of the human hepatocyte cell line HuH7"Biochemica.Biophysica.Acta. 1644. 47-59 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 森 雅博: "細胞の増殖と成長因子 1.細胞周期の解析"廣川書店. 202(18) (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujumoto, Y., Itabe, H., Mori, M., Higashi, Y., Kojima, S.Takano, T.: "Identification of the major lipid, droplet proteins of the human hepatocyte cell line HmH7"Biochemica. Biophysica. Acta. 1644. 47-59 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itabe, H., Mori, M., Fujimoto, Y., Higashi, Y., Takano, T.: "Minimally modified LDL is an oxidized LDL enriched with oxidized phosphatidyicholine"J. Biochem. (Tokyo). 134. 459-465 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higashi, Y., Itabe, H., Mori, M., Fujimoto, Y., Takano, T.: "Transmembrane lipid transfer is crucial for providing neutral lipids during VLDL assembly in endoplasmic reticulum"J. Biol Chem.. 278. 21450-21458 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Higashi, Y., Itabe, H., Fujimoto, Y., Takano T.: "Distribution of Microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells"Biochemica. Biophysica. Acta. 1581. 127-136 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itabe, H., Mori M., Fujimoto, Y., Higashi, Y., Takano, T.: "Minimally modified LDL is an oxidized LDL enriched with oxidized phosphatidylcholine"J.Biochem (Tokyo). 134. 459-465 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higashi, Y., Itabe, H., Mori, M., Fujimoto, Y., Takano T.: "Transmembrane lipid transfer is crucial for providing neutral lipids during VLDL assembly in endoplasmic reticulum"J.Biol.Chem.. 278. 21450-21458 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujimoto, Y., Itabe, H., Mori, M., Higashi, Y., Kojima, S., Takano, T.: "Identification of the major lipid droplet proteins of the human hepatocyte cell line HuH7"Biochemica.Biophysica.Acta. 1644. 47-59 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 森 雅博: "細胞の増殖と成長因子 1.細胞周期の解析"廣川書店. 202(18) (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higashi, Y., Itabe, H., Fukase, H., Mori, M., Fujimoto, Y., Sato, R., Imanaka, T, Takano, T.: "Distribution of microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells"Biochemica et Biophysica Acta. 1581. 127-136 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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