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1992 Fiscal Year Final Research Report Summary

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
Project Period (FY) 1990 – 1992
KeywordsM-CSF / atherosclerosis / cytokine / Macrophage / Smooth musclecell
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.

  • Research Products

    (12 results)

All Other

All Publications (12 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1994-03-24  

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