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

Abstract

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 preβ-1 and α-4 HDL particles, and some apoA-I was found in larger, lipid-poor, discoidal HDL particles with α-mobility. No apoC-I-containing HDL was noted, and all apoA-II and apoC-III was detected in lipid-poor, preβ-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-III was found only in small HDL with preβ-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 preβ-1 into α-4 HDL, only slight effects on apoE HDL, and no effect on apoA-IV HDL particles.

Keywords

• HDL subpopulations
• apolipoproteins
• reverse cholesterol transport