Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism
Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism
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DOI：
10.1194/jlr.m700067-jlr200
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发表时间：
2007-08-01
影响因子：
6.5
通讯作者：
Schaefer, Ernst J.
中科院分区：
文献类型：
--
作者：
Lamon-Fava, Stefania;Diffenderfer, Margaret R.;Schaefer, Ernst J.
9例高胆固醇血症和高胆固醇血症受试者入组一项随机、安慰剂对照、双盲、交叉研究，以检测阿托伐他汀20 mg/天和80 mg/天对富甘油三酯脂蛋白（TRL）、中密度脂蛋白（IDL）和LDL中载脂蛋白B-100（apo B-100）、TRL中apo B-48和HDL中apo A-I动力学的影响。与安慰剂相比，阿托伐他汀20 mg/天与TRL、IDL和LDL apoB-100池大小显著降低相关，这是由于部分分解代谢率（FCR）显著增加而不改变生成率（PR）。与20 mg/天剂量相比，阿托伐他汀80 mg/天剂量导致LDL apoB-100池大小进一步显著降低，这是FCR进一步增加的结果。两种阿托伐他汀剂量均显著降低了ApoB-48样本池大小，并且这种降低与FCR的非显著性增加相关。阿托伐他汀治疗可降低脂固醇-菜油固醇比率，该比率的变化与TRL apoB-100和apoB-48 PR的变化呈负相关。在两种剂量的阿托伐他汀下均未观察到对apoA-I动力学的显着影响。我们的数据表明，阿托伐他汀减少载脂蛋白100-和载脂蛋白48-通过增加他们的catalogue和LDL载脂蛋白100动力学具有剂量依赖性的影响。阿托伐他汀介导的胆固醇稳态变化可能有助于apo-BPR调节。
Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study to test the effect of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100 ( apoB-100) in triglyceride-rich lipoprotein (TRL), intermediate density lipoprotein ( IDL), and LDL, of apoB-48 in TRL, and of apoA-I in HDL. Compared with placebo, atorvastatin 20 mg/day was associated with significant reductions in TRL, IDL, and LDL apoB-100 pool size as a result of significant increases in fractional catabolic rate ( FCR) without changes in production rate ( PR). Compared with the 20 mg/day dose, atorvastatin 80 mg/day caused a further significant reduction in the LDL apoB-100 pool size as a result of a further increase in FCR. ApoB-48 pool size was reduced significantly by both atorvastatin doses, and this reduction was associated with nonsignificant increases in FCR. The lathosterol-campesterol ratio was decreased by atorvastatin treatment, and changes in this ratio were inversely correlated with changes in TRL apoB-100 and apoB-48 PR. No significant effect on apoA-I kinetics was observed at either dose of atorvastatin. Our data indicate that atorvastatin reduces apoB-100- and apoB-48- containing lipoproteins by increasing their catabolism and has a dose-dependent effect on LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterol homeostasis may contribute to apo-BPR regulation.