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莱西丁:胆固醇乙烯转移酶表达在活体中对巨细胞逆胆固醇运输的影响很小

Hiroyuki Tanigawa¹, Jeffrey T Billheimer, Jun-ichiro Tohyama

¹Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

|July 1, 2009

概括

莱西丁:胆固醇酸转移酶 (LCAT) 的过度表达不会增强巨细胞逆胆固醇运输 (RCT). 即使在LCAT缺乏的情况下,RCT也只减少了50%,这表明LCAT对巨细胞RCT的关键性比以前认为的要小.

科学领域:

生物化学生物化学
心血管生物学心血管生物学
代谢研究研究代谢研究

背景情况:

莱西丁:胆固醇转移酶 (LCAT) 对于血胆固醇的形成和高密度脂蛋白 (HDL) 代谢至关重要.
对于逆胆固醇输送 (RCT),即从外围组织中去除胆固醇的过程,LCAT被认为是至关重要的.

研究的目的:

为了研究LCAT在巨RCT中的精确作用.
为了确定LCAT过度表达或不足是否影响RCT率.

主要方法:

在小鼠中使用放射性标记胆固醇验证试验的量化巨细胞RCT.
在人类阿波利波蛋白AI转基因小鼠中的过度表达LCAT.
在LCAT缺陷 (LCAT(-/-)),异合体 (LCAT(+/-) 和野生类型小鼠中进行了RCT比较.

主要成果:

过度表达LCAT并没有增加巨细胞RCT,即使与食尸体受体BI或胆固醇转移蛋白的联合表达.
来自LCAT过度表达小鼠的血清显示,通过ABCA1.1.通过巨细胞促进胆固醇排放的能力降低.
在LCAT缺乏的小鼠中,尽管HDL胆固醇水平非常低,但RCT仅减少了50%.
LCAT(+/-) 小鼠保持正常的RCT与降低的HDL胆固醇.

结论:

过度表达LCAT并没有提高巨细胞RCT率.
虽然LCAT活性是完全缺乏率的限制,但RCT仅适度降低.
巨细胞RCT似乎不像以前所认为的那样依赖于LCAT活性.

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