Human lecithin:cholesterol acyltransferase deficiency: in vivo kinetics of low-density lipoprotein and lipoprotein-X.
OBJECTIVE
Lecithin:cholesterol acyltransferase deficiency (LCAT-def) is characterized by low levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) and the accumulation of lipoprotein-X (LpX). Despite the low HDL, atherosclerosis is uncommon in LCAT-def. The decreased LDL would be a possible explanation but the underlying mechanism is not clear. In addition, the mechanism(s) for LpX accumulation is not known. The aim of the present study is to elucidate the mechanism(s) responsible for the low LDL and determine the plasma kinetics of LpX in LCAT-def.


RESULTS
We conducted a radiotracer study in LCAT-def (n=2) and normal controls (n=10) and a stable isotope study in one patient and other controls (n=7). LCAT-def LDL was catabolized faster than control LDL in the control subjects as well as in LCAT-def patients. Control LDL was catabolized faster in LCAT-def patients than the controls. The production rate of LDL apolipoprotein B-100 was normal in LCAT-def. The increased LDL apoB-100 catabolism was confirmed by a stable isotope study. LpX was catabolized more slowly in LCAT-def.


CONCLUSIONS
The decreased LDL in LCAT-def is attributable to an increased catabolism caused by a rapid catabolism of abnormal LDL and an upregulation of LDL receptor pathway. The decreased catabolism of LpX contributes to its accumulation in LCAT-def.
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. masato@hi-ho.ne.jp
Masato
M
Nishiwaki
Katsunori
K
Ikewaki
Giovanni
G
Bader
Hassan
H
Nazih
Minna
M
Hannuksela
Alan T
AT
Remaley
Robert D
RD
Shamburek
H Bryan
HB
Brewer
D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D007700:Kinetics; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008073:Lipoprotein-X / Q000097:blood* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011849:Radioactive Tracers
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008055:Lipids; D008073:Lipoprotein-X; D008077:Lipoproteins, LDL; D011849:Radioactive Tracers