在小鼠中,胆固醇转移蛋白的表达促进了巨细胞逆胆固醇运输
Hiroyuki Tanigawa1, Jeffrey T Billheimer, Jun-ichiro Tohyama
1Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, USA.
Circulation
|August 22, 2007
概括
在小鼠中,胆固醇转移蛋白 (CETP) 表达增强了巨细胞逆胆固醇转移 (RCT). 这种效应取决于低密度脂蛋白受体,并有利于患有 scavenger受体B类,I型缺陷的小鼠.
科学领域:
- 脂质代谢和心血管研究.
- 分子生物学和基因工程.
- 脂蛋白相互作用的生物化学.
背景情况:
- 胆固醇转移蛋白 (CETP) 促进了脂蛋白之间的脂质转移.
- 在逆胆固醇运输 (RCT) 中CETP的确切作用尚未完全理解.
- 小鼠自然缺乏CETP,因此它们成为研究CETP功能的一个模型.
研究的目的:
- 为了研究CETP表达对巨细胞RCT in vivo的影响.
- 为了确定CETP介导的RCT对特定受体的依赖性.
- 阐明CETP在受损RCT条件中的作用.
主要方法:
- 腺相关病毒血清型8 (AAV8) 载体用于小鼠肝脏特异性CETP表达.
- 在RCT测量中使用放射标记的巨细胞进行了验证的体内测试.
- 在野生类型,低密度脂蛋白受体-零和食尸受体B类型I-零小鼠中进行了分析.
主要成果:
- 在野生类型小鼠中,CETP表达降低了高密度脂蛋白胆固醇,但增加了便中的固醇分泌.
- 在低密度脂蛋白受体-零小鼠中,CETP表达降低了高密度脂蛋白胆固醇,但没有对便中的固醇分泌产生影响.
- 在CETP表达降低了高密度脂蛋白胆固醇,增加了便中的固醇分泌在食尸体受体B类,I型-null小鼠.
结论:
- 在小鼠中,CETP表达促进了巨细胞RCT.
- CETP对RCT的影响取决于低密度脂蛋白受体.
- CETP可以恢复被损坏的RCT在食尸体受体B类,I型缺陷小鼠中.
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