Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes.

Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes.
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使用稳定同位素研究人载脂蛋白 A-I 与载脂蛋白 B-48 和 B-100 动力学之间的相互关系。

DOI:
10.1161/01.atv.0000137975.14996.df
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发表时间:
2004
期刊:
Arteriosclerosis, thrombosis, and vascular biology.
影响因子:
--
通讯作者:
Schaefer,ErnstJ
Schaefer,ErnstJ
中科院分区:
--
文献类型:
--
作者:
Welty,FrancineK;Lichtenstein,AliceH;Barrett,PHughR;Dolnikowski,GregoryG;Schaefer,ErnstJ

文献摘要

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方法和结果-高密度脂蛋白(HDL)内的载脂蛋白(apo)A-I、富含甘油三酯的脂蛋白内的apoB-48和apoB-100的动力学,和载脂蛋白B-100在中密度脂蛋白和低密度脂蛋白(LDL)的检查与启动恒定输注[5,5,5- 2 H3]亮氨酸在进食状态下(每小时进食)在23名受试者消耗36%的总脂肪饮食后。通过超离心分离脂蛋白;通过SDS-PAGE凝胶分离载脂蛋白;通过气相色谱/质谱法评估同位素富集。通过SAAM II数据的多房室模型计算动力学参数。ApoA-I生成率(PR)与LDL apoB-100池大小相关(PS;r=0.49;P=0.017)和LDL胆固醇apoA-I分解率与apoB-48分解率呈负相关(r=0.61;P=0.002)。(r=-0.40;P=0.05),但与极低密度脂蛋白apoB-100 FCR无关。结论apoA-I和apoB动力学之间存在两种联系:1)低密度脂蛋白apoB-100 PS高时,apoA-Ⅰ PR增高;乳糜微粒残留清除延迟(由apoB-48 FCR表示)与增强的apoA-I FCR相关,这一发现表明肠道脂蛋白的变化在决定HDL胆固醇水平方面可能比肝脏的变化更重要,脂蛋白
Objective—Our purpose was to determine the relationship between apolipoprotein (apo) A-I and apoB-48 and apoB-100 metabolism in moderately hypercholesterolemic humans.Methods and Results—The kinetics of apoA-I within high-density lipoprotein (HDL), apoB-48 and apoB-100 within triglyceride-rich lipoproteins, and apoB-100 within intermediate-density lipoprotein and low density-lipoprotein (LDL) were examined with a primed constant infusion of [5,5,5-2H3] leucine in the fed state (hourly feeding) in 23 subjects after consumption of a 36% total fat diet. Lipoproteins were isolated by ultracentrifugation; apolipoproteins by SDS-PAGE gels; and isotope enrichment assessed by gas chromatograph/mass spectrometry. Kinetic parameters were calculated by multicompartmental modeling of the data with SAAM II. ApoA-I production rate (PR) was correlated with LDL apoB-100 pool size (PS;r=0.49;P=0.017) and LDL cholesterol (r=0.61;P=0.002), whereas apoA-I fractional catabolic rate (FCR) was inversely correlated with apoB-48 FCR (r=−0.40;P=0.05) but not with very low-density lipoprotein apoB-100 FCR.Conclusions—Two links exist between apoA-I and apoB kinetics: 1) when LDL apoB-100 PS is high, there is increased apoA-I PR; and 2) delayed chylomicron remnant clearance (represented by apoB-48 FCR) is associated with enhanced apoA-I FCR, a finding indicating that alterations in intestinal lipoproteins may be more important in determining HDL cholesterol levels than changes in liver lipoproteins.