1992 Fiscal Year Final Research Report Summary
Therapeutic trial of atherosclerosis by M-CSF
| Project/Area Number |
02557110
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | University of Tokyo |
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Principal Investigator |
YAMADA Nobuhiro Univ.of Tokyo, Faculty of Med. Assist.Prof., 医学部(病), 助手 (40200729)
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| 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
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| Project Period (FY) |
1990 – 1992
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| Keywords | M-CSF / atherosclerosis / cytokine / Macrophage / Smooth musclecell |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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
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