权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Therapeutic strategy for atherosclerosis targeting for CETP

以CETP为靶点的动脉粥样硬化治疗策略

基本信息

批准号：
12670712
负责人：
SAKU Keijiro
金额：
$ 2.05万
依托单位：
Fukuoka University
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
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670712/
关键词：
High density lipoprotein apo HDL kinetics CETP Apolipoprotein A-l CETP inhibitor apo A-l mRNA 生対内アポHDL代謝回転アポリポ蛋白A-1 アポA-1 mRNA アポリポ蛋白 A-I SRB1 ヒトCETP-Tgマウス

项目摘要

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.

背景：CETP在胆固醇逆向转运中起重要作用。CETP抑制剂JTT-705抑制CETP活性，增加血清载脂蛋白a - 1水平，抑制动脉粥样硬化。为了阐明抑制CETP增加HDL水平的机制，我们研究了JTT-705对胆固醇喂养家兔体内载脂蛋白a - 1动力学特性的影响。方法：随机选取日本大白兔，分别饲喂(a)正常兔粮LRC-4 （n=10）、(b)含0.2%胆固醇的日粮（n=9）或(c) (b)与0.75% JTT-705的混合物（n=7） 7个月，测定CETP活性和血清脂蛋白水平。体内载脂蛋白a - 1动力学在研究结束时通过注射放射性碘化载脂蛋白a - 1进行。结果：JTT-705对高胆固醇家兔CETP活性有38.5%的抑制作用。与正常喂养相比，胆固醇喂养降低了SR[8.3±1.1比10.1±1.8 mg/Kg/d]和血清载脂蛋白a - 1水平，增加了FCR[0.61±0.07比0.52±0.09 /d]。JTT-705使高胆固醇家兔SR（11.2±2.9 mg/Kg/day）和载脂蛋白a - 1 （apo a - 1）水平降低，FCR（0.50±0.06 mg/ day）升高。结论：抑制CETP活性有利于胆固醇喂养家兔的脂蛋白代谢，提示抑制CETP可能是一种治疗动脉粥样硬化的方法。