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Therapeutic strategy for atherosclerosis targeting for CETP

Therapeutic strategy for atherosclerosis targeting for CETP
以CETP为靶点的动脉粥样硬化治疗策略
批准号:
12670712
负责人:
SAKU Keijiro
金额:
$2.05万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 2002

项目摘要

项目成果

SAKU Keijiro的其他基金

相关文献

中文摘要
翻译
背景:CETP在胆固醇逆向转运中起重要作用。CETP抑制剂JTT-705对CETP活性的抑制增加血清apo A-I水平并抑制动脉粥样硬化。为了阐明CETP抑制增加HDL水平的机制,我们检查了JTT-705对胆固醇喂养的兔中apo A-I的体内动力学性质的影响。研究方法:随机选择日本白色家兔,以(a)正常兔饲料LRC-4(n=10),(B)含0.2%胆固醇的饲料(n=9),或(c)(B)和0.75% JTT-705的混合物(n=7)喂养7个月。测定CETP活性和血清脂蛋白水平。通过在研究结束时注射放射性碘标记的apo A-I进行体内apo A-I动力学。结果:JTT-705对胆固醇喂养家兔的CETP活性抑制率为38.5%。与正常饲料喂养相比,胆固醇喂养降低SR [8.3 ± 1.1 vs. 10.1 ± 1.8 mg/Kg/d]和血清apo A-1水平,并增加FCR [0.61 ± 0.07 vs. 0.52 ± 0.09 /d]。JTT-705使胆固醇喂养家兔中降低的SR [11.2 ± 2.9 mg/Kg/天]和血清apo A-I水平以及升高的FCR [0.50 ± 0.06 /天]正常化。结论:CETP活性的抑制有利地影响胆固醇喂养的兔中的脂蛋白代谢,这表明CETP抑制可能是动脉粥样硬化的治疗方法。
英文摘要
Background: CETP plays an important role in the reverse cholesterol transport. Inhibition of CETP activity by a CETP inhibitor, JTT-705, increases serum apo A-l levels and inhibits atherosclerosis. To clarify the mechanism by which CETP inhibition increases HDL levels, we examined the effects of JTT-705 on the in vivo kinetics properties of apo A-l in cholesterol-fed rabbits. Methods: Japanese White rabbits were randomly selected to be fed with (a) a normal rabbit chow, LRC-4 (n=10), (b) a diet containing 0.2% cholesterol (n=9), or (c) admixture of (b) and 0.75% JTT-705 (n=7) for 7 mo. CETP activities and serum levels of lipoproteins were measured. In vivo apo A-l kinetics was performed by injecting radioiodinated apo A-l at the end of the study. Results: JTT-705 inhibited 38.5% of the CETP activity in cholesterol-fed rabbits. Cholesterol-feeding decreased SR [8.3 ± 1.1 vs. 10.1 ± 1.8 mg/Kg/day] and serum levels of apo A-l and increased FCR [0.61 ± 0.07 vs. 0.52 ± 0.09 /day] compared with normal chow-feeding. JTT-705 normalized the reduced SR [11.2 ± 2.9 mg/Kg/day] and serum levels of apo A-l and the increased FCR [0.50 ± 0.06 /day] in cholesterol-fed rabbits. Conclusion: Inhibition of CETP activity favorably affects the lipoprotein metabolism in cholesterol-fed rabbits, suggesting that CETP inhibition may be a therapeutic approach for atherosclerosis.
期刊论文(32)
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会议论文
朔啓二郎: "HDL代謝と虚血性心臓病"臨床と研究. 78巻1号. 135-139 (2001)
Keijiro Saku:“HDL 代谢与缺血性心脏病”,《临床与研究》,第 78 卷,第 1. 135-139 期(2001 年)。
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Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi A, Arai H.: "Serum lysophosphatidic acid is produced through diverse phospholipase pathways"J Biol Chem.. 277. 48737-48744 (2002)
Aoki J、Taira A、Takanezawa Y、Kishi Y、Hama K、Kishimoto T、Mizuno K、Saku K、Taguchi A、Arai H.:“血清溶血磷脂酸是通过多种磷脂酶途径产生的”J Biol Chem.. 277. 48737
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Zhang B, Shimoji E, Tanaka H, Saku K: "Evaluation of apolipoprotein A-l kinetics in rabbits in vivo using in situ and exogeneous radioiodination methods"Lipid. in press. (2003)
张 B、Shimoji E、田中 H、Saku K:“使用原位和外源放射性碘标记方法评估兔子体内载脂蛋白 A-l 动力学”脂质。
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Nomoto J, Oku K, Takao M, Tahara H, Inoue T, Handa K, Arakawa K, Saku K: "Left arterial thrombus formation in patients with nonvalvular paroxysmal atrial fibrillation"Med Bull Fukuoka Univ.. 29(4). 187-194 (2002)
Nomoto J,Oku K,Takao M,Tahara H,Inoue T,Handa K,Arakawa K,Saku K:“非瓣膜性阵发性心房颤动患者的左动脉血栓形成”Med Bull Fukuoka Univ.. 29(4)。
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29
    New diagnostic and therapeutic strategies for atherosclerosis using newly developed apolipoprotein A-I mimetic peptide
    • 批准号:
      24591123
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $3.24万
    • 财政年份:
      2012
    • 负责人:
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    • 依托单位:
    Possibility of drug discovery : Development of new peptide type of reconstituted HDL
    • 批准号:
      21590960
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.75万
    • 财政年份:
      2009
    • 负责人:
      SAKU Keijiro
    • 依托单位:
    Advanced medical technology on cardiovascular disease- Elucidation of the molecular mechanism and the application on various pathological conditions for the establishment of HDL therapy
    • 批准号:
      18590826
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.56万
    • 财政年份:
      2006
    • 负责人:
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    • 依托单位:
    Quality, function and genetic assessments of NO, ACE and HDL in patients with coronary artery disease
    • 批准号:
      09670773
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
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    • 财政年份:
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    • 负责人:
      SAKU Keijiro
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