Role of LCAT in HDL remodeling: investigation of LCAT deficiency states
Role of LCAT in HDL remodeling: investigation of LCAT deficiency states
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DOI：
10.1194/jlr.m600403-jlr200
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发表时间：
2007-03-01
影响因子：
6.5
通讯作者：
Calabresi, Laura
中科院分区：
文献类型：
--
作者：
Asztalos, Bela F.;Schaefer, Ernst J.;Calabresi, Laura
为了更好地理解LCAT在HDL代谢中的作用，我们比较了纯合型（n = 11）和杂合型（n = 11）LCAT缺乏症受试者与对照组（n = 22）的HDL亚群。评估了载脂蛋白A-I（apoA-I）-、apoA-II-、apoA-IV-、apoC-I-、apoC-III-和含apoE的HDL亚群的分布和浓度。与对照组相比，纯合子和杂合子的LCAT质量（-77%和-13%）和LCAT活性（-99%和-39%）分别较低。在纯合子中，大多数apoA-I存在于小的、盘状的、脂化差的前β-1和α-4 HDL颗粒中，一些apoA-I存在于较大的、脂性差的、具有α-迁移率的盘状HDL颗粒中。未观察到含apoC-I的HDL，并且在贫脂质、准备流动性颗粒中检测到所有apoA-H和apoC-M。载脂蛋白E颗粒比正常颗粒更分散。含ApoA-IV颗粒正常。杂合子的配置文件类似于控制，除了apoC-M被发现只在小HDL与prep流动性。我们的数据与以下概念一致：1）LCAT活性对于形成大的、球形的、含apoA-I的HDL和形成正常大小的apoC-I和apoC-III HDL是必不可少的; 2）对前β-I转化为α-4 HDL几乎没有影响，对apoE HDL只有轻微影响，对apoA-IV HDL颗粒没有影响。
To better understand the role of LCAT in HDL metabolism, we compared HDL subpopulations in subjects with homozygous (n = 11) and heterozygous (n = 11) LCAT deficiency with controls (n = 22). Distribution and concentrations of apolipoprotein A-I (apoA-I)-, apoA-II-, apoA-IV-, apoC-I-, apoC-III-, and apoE-containing HDL subpopulations were assessed. Compared with controls, homozygotes and heterozygotes had lower LCAT masses (-77% and -13%), and LCAT activities (-99% and -39%), respectively. In homozygotes, the majority of apoA-I was found in small, disc-shaped, poorly lipidated pre beta-1 and alpha-4 HDL particles, and some apoA-I was found in larger, lipid-poor, discoidal HDL particles with a-mobility. No apoC-I-containing HDL was noted, and all apoA-H and apoC-M was detected in lipid-poor, prep-mobility particles. ApoE-containing particles were more disperse than normal. ApoA-IV-containing particles were normal. Heterozygotes had profiles similar to controls, except that apoC-M was found only in small HDL with prep-mobility. Our data are consistent with the concepts that LCAT activity: 1) is essential for developing large, spherical, apoA-I-containing HDL and for the formation of normal-sized apoC-I and apoC-III HDL; and 2) has little affect on the conversion of pre beta-I into alpha-4 HDL, only slight effects on apoE HDL, and no effect on apoA-IV HDL particles.