Therapeutic trial of atherosclerosis by M-CSF

M-CSF 治疗动脉粥样硬化的试验

• 批准号: 02557110
• 负责人: YAMADA Nobuhiro
• 金额: $ 9.47万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02557110/
• 关键词: M-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

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.

早期动脉粥样硬化病变以巨噬细胞衍生泡沫细胞的存在为特征。巨噬细胞集落刺激因子（M-CSF）特异性刺激单核巨噬细胞的功能。为了阐明M-CSF在体内动脉粥样硬化过程中的作用，我们将重组人M-CSF注入家族性高胆固醇血症动物模型Watanabe遗传性高脂血症（WHHL）兔。将300微克M-CSF静脉注射2.5月龄WHHL兔，每周3次，持续8.5个月。经M-CSF治疗后，我们发现动脉粥样硬化的进展非常缓慢。与对照组（4.32 * 0.61 mg/g）相比，m - csf处理动物主动脉中胆固醇酯的积累明显减少（0.60 * 0.32 mg/g组织）。此外，M-CSF治疗动物的主动脉表面有宏观斑块的百分比为14.3 * 6.2%，远低于接受生理盐水注射的对照组（38.8 * 8.0%）。因此，M-CSF通过影响巨噬细胞功能，明确地阻止了WHHL家兔动脉粥样硬化的进展。

项目成果

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)

Hitoshi Shimano、Nobuhiro Yamada 等人：“转基因小鼠中载脂蛋白 E 过度表达；除高密度脂蛋白外的脂蛋白显着减少”Proc.Natl.Acad.Sci USA (1992)。

山田 信博他: "Macrophage colong stimalating factor prevents the progression of atheros clerosis in WHHL rabbits" Atherosclerosis. 93. 245-54 (1992)

Nobuhiro Yamada 等人：“巨噬细胞结肠刺激因子可预防 WHHL 兔子中动脉粥样硬化的进展”，动脉粥样硬化。

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 hyperli

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：“巨噬细胞集落刺激因子可防止

山田 信博 他: "Macrophage colony stimulating factor prevants the progression of atherosclerosis in WHHL rafbits" Athierosclerosis. 93. 245-54 (1992)

Nobuhiro Yamada 等人：“巨噬细胞集落刺激因子预防 WHHL rafbit 中动脉粥样硬化的进展”Athierosclerosis。

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)

Takaya Gotoda、Nobuhiro Yamada 等人：“供体剪接位点突变出现多个异常剪接 mRNA，导致家族性脂蛋白脂肪酶缺乏。”J.Biol.Chem.24757-24762 (1991)。