Increased production of VLDL apoB-100 in subjects with familial hypercholesterolemia carrying the same null LDL receptor gene mutation
Increased production of VLDL apoB-100 in subjects with familial hypercholesterolemia carrying the same null LDL receptor gene mutation
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DOI：
10.1194/jlr.m300448-jlr200
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发表时间：
2004-05-01
影响因子：
6.5
通讯作者：
Couture, P
中科院分区：
文献类型：
--
作者：
Tremblay, AJ;Lamarche, B;Couture, P
早期的放射动力学研究表明，家族性高胆固醇血症(FH)患者的典型代谢缺陷是由于低密度脂蛋白受体活性降低导致的低密度脂蛋白分解代谢。然而，最近的研究表明，肝脏过度分泌载脂蛋白B-100(apoB-100)也可能是FH患者血浆低密度脂蛋白显著升高的原因之一。本研究的目的是检测稳定同位素(L-[5，5，5-D-3]亮氨酸)标记的载脂蛋白B-100在5名正常血脂对照组和7名有良好特征的FH受试者中的动力学。与对照组相比，FH杂合子和FH纯合子的VLDL apoB-100生成率分别增加了50%和109%。此外，FH受试者的低密度脂蛋白apoB-100池大小显著高于对照组，而低密度脂蛋白apoB-100的分解率低于对照组。这些结果表明，FH患者血浆低密度脂蛋白-胆固醇的升高既可归因于低密度脂蛋白清除率的降低，也可归因于肝脏中含有apoB-100的脂蛋白产量的增加。霍格、J.Bergeron、C.Gagne和V Couture。携带同样为零的低密度脂蛋白受体基因突变的家族性高胆固醇血症患者的极低密度脂蛋白载脂蛋白B-100的产生增加。45：866-872。
Early radiokinetic studies revealed that the classical metabolic defect in patients with familial hypercholesterolemia (FH) is hypocatabolism of LDL due to decreased LDL receptor activity. However, recent studies have suggested that hepatic oversecretion of apolipoprotein B-100 (apoB-100)-containing lipoproteins could also contribute to the markedly elevated plasma concentrations of LDL-cholesterol found in FH. The aim of this study was to examine the kinetics of apoB-100 labeled with a stable isotope (L-[5,5,5-D-3] leucine) in five normolipidemic controls and in seven well-characterized FH subjects that included six FH heterozygotes and one FH homozygote carrying the same null LDL receptor gene mutation. As compared with controls, the VLDL apoB-100 production rate was increased by 50% in the FH heterozygotes and by 109% in the FH homozygote. Furthermore, FH subjects had significantly higher LDL apoB-100 pool size and lower LDL apoB-100 fractional catabolic rate than controls.jlr These results indicate that the elevation of plasma LDI-cholesterol found in FH is attributable to both decreased clearance of LDL and increased hepatic production of apoB-100-containing lipo-proteins.-Tremblay, A. J., B. Lamarche, I. L. Ruel, J-C. Hogue,.J. Bergeron, C. Gagne, and V Couture. Increased production of VLDL apoB-100 in subjects with familial hypercholesterolemia carrying the same null LDL receptor gene mutation.J. Lipid Res. 2004. 45: 866-872.