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Therapeutic trial of atherosclerosis by M-CSF

Research Project

Project/Area Number 02557110
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionUniversity of Tokyo

Principal Investigator

YAMADA Nobuhiro  Univ.of Tokyo, Faculty of Med. Assist.Prof., 医学部(病), 助手 (40200729)

Co-Investigator(Kenkyū-buntansha) WATANABE Yoshiro  Junten Med.School physician, 医学部(病), 医員
HARADA Kenji  Univ.of Tokyo, Faculty of Med. physician, 医学部(病), 医員
GOTODA Takanari  Univ.of Tokyo, Faculty of Med. physician, 医学部(病), 医員
SHIMANO Hitoshi  Univ.of Tokyo, Faculty of Med. physician, 医学部(病), 医員
杢野 浩司  順天堂大学, 医学部, 医員
石橋 俊  東京大学, 医学部, 助手
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1990: ¥9,200,000 (Direct Cost: ¥9,200,000)
KeywordsM-CSF / atherosclerosis / cytokine / Macrophage / Smooth musclecell / WHHLウサギ / MーCSF / マクロファ-ジ / 動脈硬化症 / コレステロ-ル / スキャベンジャ-受容体
Research Abstract

The early atherosclerotic lesion id characterized by the presence of macrophage-derived foam cells. Macrophage colony stimulating factor (M-CSF) specifically stimulates the functions of the monocyte-macrophages. To elucidate the effects of M-CSF in the atherogenic process in vivo, we administered human recombinant M-CSF into Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Three hundred micrograms of M-CSF were intravenously injected into WHHL rabbits aged 2.5 months, three times a week for 8.5 months. After the M-CSF treatment, we found very retarded progression of atherosclerosis. The accumulation of cholesterol ester was remarkably decreased in the aortae of M-CSF-treated animals (0.60 * 0.32 mg/g tissue), as compared to those of controls (4.32 * 0.61 mg/g tissue). Furthermore, the percentage of the surface area of the aorta with macroscopic plaque in animals treated with M-CSF was 14.3 * 6.2%, much less than that in controls receiving saline injection (38.8 * 8.0%). Thus, M-CSF definitely prevented the progression of atherosclerosis in WHHL rabbits by influencing macrophage functions.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 島野 仁他: "Orerexpression of apo E in trausgenic mice:A marked reduction in plaswa lipoprotein" Proc,Natl,Acad,Sci USA. 89. 1750-54 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山田 信博他: "Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived fromarteriosclerotic" J.Biol chem. 267. 5693-99 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山田 信博他: "Apolipoprotein E prevents the progression of artero sclerosis in u'HHL rabbgits." J.clin.Invest. 89. 706-11 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山田 信博他: "PDGF induces c-fms and scavenger recepter genes in vascular smooth muscle cells" J.Biol.chem. 267. 13107-12 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山田 信博他: "Macrophage colong stimalating factor prevents the progression of atheros clerosis in WHHL rabbits" Atherosclerosis. 93. 245-54 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山田 信博他: "PDGF BB deincer suppresses the expression of macrophage colony stimulating factor in buman" J.Biol chem. 267. 15455-58 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H Shimano, M Katsuki, M Shimada, Ta Gotoda, K Harada, T Murase, C Fukazawa, F Takaku, Y Yazaki, N Yamada: "Overexpression of A polipoprotein E in Transgenic Mice: A Marked Reduction in Plasma Lipoproteins except High Density Lipoprotein" Proc Natl Acad Sci USA.89. 1750-1754 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T Inaba, N Yamada, T Gotoda, H Shimada, T Dadowaki, K Momomura, K Motoyoshi, T Tsukada, N Morisaki, Y Saito, S Yoshida, F Takaku, Y Yazaki: "Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived from arteriosclerotic lesion" J Biol Chem. 267. 5693-5699 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N Yamada, I Inoue, M Kawamura, K Harada, Y Watanabe, H Shimano, T Gotoda, M Shimada, K Kozaki, T Tsukada, M Shiomi, Y Watanabe, Y Yazaki: "A polipoprotein E prevents the progression of atherosclerosis in WHHL rabbits" J Clin Invest.89. 706-711 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T Inaba, T Gotoda, H Shimano, M Shimada, K Harada, K Kozaki, Y Watanabe, E Ho, K Motoyoshi, Y Yazaki, N Yamada: "PDGF Induces c-fms and scavenger receptor genes in vascular smooth muscle cells" J Biol. Chem.267. 13107-12 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] I Inoue, T Inaba, K Motoyoshi, K Harada, H Shimano, M Kawamura, T Gotoda, T Oka, M Shiomi, Y Watanabe, T Tsukada, Y Yazaki, F Takaku, N Yamada: "Macrophage colony-stimulating factor prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits" Atherosclerosis 93. 245-254 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] M Shimada, N Yamada, T Inaba, H Shimano, T Gotoda, Y Watanabe, K Yamamoto, K Motoyoshi, Y Yazaki: "Platclet-derived growth factor BB-dimer suppresses the expression of macrophage colony-stimulating factor in human vascular smooth muscle cells" J Biol Chem. 267. 15455-15458 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 島野 仁 他: "OverexPressiov oF apo E in trausgeuic micl:A marked reduction in plaswa lipoprotein…." Broc.Natl.Acad.Sci USA. 89. 1750-54 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 信博 他: "Expression of M-CSF receotor eueoded by c-fms on smooth muscle cells derived from arteriosclerosis…." J.Biol Chem. 267. 5693-99 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 信博 他: "Apolipoprotin E preveuts the progression of arteriosclerosis in WHHL rafbits" J.Clin.lnvest.89. 706-11 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 信博 他: "PDGF induces c-fms and scavenger recepter genas in vascular smooth musicle cells" J.Biol.Chem. 267. 13107-12 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 信博 他: "Macrophage colony stimulating factor prevants the progression of atherosclerosis in WHHL rafbits" Athierosclerosis. 93. 245-54 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 信博 他: "PDGF BB deincer seeppressos the expression of macroplage colony stimulating factor buman…." J.Biol.Chem. 267. 15455-58 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 信博 他: "Apolipoprotein E prevents the progression of athero sclerosis in WHHL rabbits." J,Clin.lnvest.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 稲田 寿守,山田 信博 他: "Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived from arterio sclesotic lesion" J.Biol.Chem.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 後藤田 貴也,山田 信博 他: "Occurence of Multiple Aberrantly-spliced mRNAs upon a donor splice sito mutation that causes familial lipoprotein lipase deficiency." J.Biol.Chem.266. 24757-24762 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 島野 仁,山田 信博 他: "Overexpression of apolipoprotein E in transgenic mice;Amarked reduction in plorma lipoproteins except high density lipoprotein" Proc.Natl.Acad.Sci USA. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 後藤田 貴也,山田 信博 他: "Differential phenotypic expression by three separate mutant alleles in familial lecitlein cholesterol acyltransferase(LCAT)deficieney" Lancet. 338. 778-781 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 後藤田 貴也,山田 信博 他: "Heterogenous mutations in the human lipoprotein lipuse gene in patients with familial lipoprotein lipase" J.Clin.lnvest.88. 1856-1864 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 島野 仁,山田 信博他: "Plasma cholesterolーlowering activity of MーCSF" Ann.NY Acad.Sci. 587. 362-370 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 島野 仁,山田 信博他: "Human mouocyteーcolony stimulating factor enbances the clcarauee of lipoproteins contoining apoB100" J.Biol.Chem.265. 12869-75 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 石橋 俊,山田 信博他: "Monocyte colonyーstimuloting factor enhances uptake and degradation of actylated low deusity lipoproteins" J.Biol.Chem.265. 14109-17 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 石橋 俊,山田 信博他: "Effect of MーCSF on lipeprotein metakolism" Ann NY Acad Sci in press. (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 石橋 俊,山田 信博他: "Apolipoprotein E and lipeprotein lipase secreted from buman monocytederived maeropbages modulate VLDL uptake" J.Biol.Chem.265. 3040-7 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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