on March 16, 2006
Published online before print March 16, 2006, doi: 10.1161/01.ATV.0000217910.90210.99
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Submitted on October 18, 2005
Accepted on March 1, 2006
Human Lecithin:Cholesterol Acyltransferase Deficiency. In Vivo Kinetics of Low-Density Lipoprotein and Lipoprotein-X
Masato Nishiwaki *;
From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. Current affiliation for M.N.: First Department of Internal Medicine, National Defense Medical College, Saitama, Japan. Current affiliation for K.I.: Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
* To whom correspondence should be addressed. E-mail: masato{at}hi-ho.ne.jp.
Objectives--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.
Methods and 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 caused by 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.
Key words: lecithin:cholesterol acyltransferase • low-density lipoprotein • lipoprotein-X • kinetics • stable isotope
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