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Study on lipid metabolism and atherogenesis with transgenic mouse models

Research Project

Project/Area Number 07044254
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

YOKODE Masayuki  Graduate school of Medicine, Kyoto University, 医学研究科, 講師 (20252447)

Co-Investigator(Kenkyū-buntansha) MAEDA Nobuyo  University of North Carolina, 医学部, 助教授
RUBIN Edward M  University of California at Berkeley, 医学部, 主任研究員
IEHARA Noriyuki  Graduate school of Medicine, Kyoto University, 医学研究科, 助手 (20281727)
DOI Toshio  Graduate school of Medicine, Kyoto University, 医学研究科, 講師 (60183498)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsHyperlipidemia / Atherosclerosis / apolipoprotein E / apo (a) / Knockout mouse / Transgeric Mouse / 粥上動脈硬化
Research Abstract

In the current study, we investigated the molecular mechanism of atherogenesis by using molecular biology and mouse biology. [1] The low density lipoprotein receptor is known to play a key role in regulation of the levels of plasma cholesterol. Yokode, the head investigator of current study, has previously shown that the liver has a unique molecular system to transfer the LDL receptor. To examine further the molecular mechanism of this trafficking pathway, a new transgenic mice expressing a missorted LDL receptor molecule, which could be distinguished from the wild type receptor. We are now studying the pathway for the receptor in the hepatocyte of this mouse. [2] By collaboration with Drs.Maeda and Rubin, we studied molecular mechanism for accumulation of foam cells, a typical feature of early lesion of atheroscleosis in apoE knockout mice. By injection with the antagonizing rat monoclonal antibody against murine c-fms, the receptor for macrophage colony stimulating factor (M-CSF), we demonstrated that M-CSF/c-fms has an essential role in the development of atheroma in these mice. [3] We also obtained apo (a) transgenic mive to study the effect of apo (a) on atherogenesis and vascular remodeling. [4] In order to conduct these experiments, we presented our data in American Heart Association Meeting held in New Orleans in November, 1996, and discussed with the two investigators.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Murayama,T.,Yokode,M.,Yoshida,H.et al.: "Inhibition of atherogenesis in apolipoproetin E-deficient mice injected with the antagonistic monoclonal antibody against murine c-fms,the receptor for macrophage cology stimulating factor" Circulation. 94(8). 1-633 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yokode,M.,Ueyama,K.,Nagano,Y.et al.: "Modification of hygh-and low-density lipoproteins by cigarette smoke oxidants." Ann.N.Y.Acad.Scl.786. 245-251 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morrison,J.R.,Paszty,C.,Stevens,M.E.et al.: "Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism." Proc.Natl.Acad.Sci.U.S.A.93(14). 7154-7259 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gong,E.L.,Stolzfus,L.J.,Brion,C.M.et al.: "Contrasting in vivo effects of murine and human apolioprotein A-II." J.Biol.Chem.271(11). 5984-5987 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kobayashi,J.,Applebaum-Bowden,D.,Dogi,K.A.et al: "Analysis of protein structure-function in vivo.Adenovirus-mediated transfer of lipase lid mutants in hepatic lipase-deficient mice." J.Biol.Chem.271(42). 26296-26301 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Applebaum-Bowden,D.,Kobayashi,J.,Kashgap,V.S.et al: "Hepatic lipase gene therapy in hepatic lipase-deficient mice.Adenovirus-mediated replacement of a lipolytic enzyme to the vascular endothelium." J.Clin.Invest.97(3). 799-805 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murayama, T.et al.: "Inhibition of atherogenesis in apolipoproetin E-deficient mice injected with the antagonistic monoclonal antibody against murine c-fms, the receptor for macrophage colony stimulating factor" Circulation. 94. I633 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yokode, et al.: "Modification of high- and low- density lipoproteins by cigarette smoke oxidants." Ann.N.Y.Acad.Sci.786. 245-251 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morrison, J.R.et al.: "Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism." Proc.Natl.Acad.Sci.U.S.A.93. 7154-7159 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Gong, E.L.et al.: "Contrasting in vivo effects of murine and human apolioprotein A-II." J.Biol.Chem.271. 5984-5987 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] "Analysis of protein structure-function in vivo. Adenovirus-mediated transfer e lid mutants in hepatic lipase-deficient mice." J.Biol.Chem.271. 26296-26301 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Applebaum Bowden, D.et al.: "Hepatic lipase gene therapy in hepatic lipase-deficient mice. Adenovius-mediated replacement of a lipolytic enzyme to the vascular endothelium." J.Clin.Invest.97. 799-805 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murayama,T.,Yokode,M,Yoshida,H.et al.: "Inhibition of atherogenesis in apolipoproetin E-deficient mice injected with the antagonistic monoclonal antibody against murine c-fms,the receptor for macrophage colony stimulating factor" Circulation. 94(8). 1-633 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokode,M.,Ueyama,K.,Nagano,Y.et al.: "Modification of high-and low-density lipoproteins by cigaratte smoke oxidants." Ann.N.Y.Acad.Sci.786. 245-251 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morrison,J.R.,Paszty,C.,Stevens,M.E.et al.: "Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism." Proc.Natl.Acad.Sci.U.S.A.93(14). 7154-7159 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Gong,E.L.,Stolzfus,L.J.,Brion,C.M.et al.: "Contrasting in vivo effects of murine and human apolioprotein A-II." J.Biol.Chem.271(11). 5984-5987 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kobayashi,J.,Applebaum-Bowden,D.,Dogi,K.A.et al.: "Analysis of protein structure-function in vivo.Adenovirus-mediated transfer of lipase lid mutants in hepatic lipase-deficient mice." J.Biol.Chem.271(42). 26296-26301 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Applebaum-Bowden,D.,Kobayashi,J.,Kashgap,V.S.et al: "Hepatic lipase gene therapy in hepatic lipase-deficient mice.Adenovirus-mediated replacement of a lipolytic enzyme to the vascular endothelium." J.Clin.Invest.97(3). 799-805 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokode, M. and Kita, T.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yokode, Y., Nagano, Y., Arai, H. et al.: "Cigarette smoke and lipoprotein modification: a possible interpretation for development of atherosclerosis" Ann. N. Y. Acad. Sci.748. 294-360 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka, M., Otani, H., Yokode, M. et al.: "Reguation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia." Atherosclerosis. 114. 73-82 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ochi, H, Kume, N., Nishi, E. etal..: "Elevated levels of cAMP inhibit protein kinase C…independent mechanisms of endothelial platelet‐derived growth factor‐B chain and intercellular adhesion molecule‐1 gene induction by lysophosphatidylcholine." Circ‐Res.77. 530-535 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kume, N., Ochi, H., Nishi, E. et al.: "Involvement of protein kinase C‐independent mechanisms in endothelial ICAM‐1 up‐regulation by lysophosphatidycholine." Ann‐N‐Y‐Acad‐Sci.748. 541-542 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 森崎信尋、佐藤靖史、横出正之 共編: "分子動脈硬化学" メディカルレビュー社, 361 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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