Role of LCAT in HDL remodeling: investigation of LCAT deficiency states

被引:141
作者
Asztalos, Bela F. [1 ]
Schaefer, Ernst J.
Horvath, Katalin V.
Yamashita, Shizuya
Miller, Michael
Franceschini, Guido
Calabresi, Laura
机构
[1] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr, Lipid Metab Lab, Boston, MA 02111 USA
[2] Osaka Univ, Dept Internal Med & Mol Sci, Suita, Osaka 565, Japan
[3] Univ Maryland, Dept Med, Baltimore, MD 21201 USA
[4] Univ Milan, Ctr E Grossi Paoletti, Dept Pharmacol Sci, I-20122 Milan, Italy
关键词
HDL subpopulations; apolipoproteins; reverse cholesterol transport;
D O I
10.1194/jlr.M600403-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:592 / 599
页数:8
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