Role of LCAT in HDL remodeling: investigation of LCAT deficiency states.
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 prebeta-1 and alpha-4 HDL particles, and some apoA-I was found in larger, lipid-poor, discoidal HDL particles with alpha-mobility. No apoC-I-containing HDL was noted, and all apoA-II and apoC-III was detected in lipid-poor, prebeta-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 prebeta-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 prebeta-1 into alpha-4 HDL, only slight effects on apoE HDL, and no effect on apoA-IV HDL particles.
Asztalos
Bela F
BF
Lipid Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. bela.asztalos@tufts.edu
Schaefer
Ernst J
EJ
Horvath
Katalin V
KV
Yamashita
Shizuya
S
Miller
Michael
M
Franceschini
Guido
G
Calabresi
Laura
L
D000704:Analysis of Variance; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D053302:Apolipoprotein C-I / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D001054:Apolipoproteins A / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053302:Apolipoprotein C-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase