Dose-dependent effect of rosuvastatin on apolipoprotein B-100 kinetics in the metabolic syndrome
Dose-dependent effect of rosuvastatin on apolipoprotein B-100 kinetics in the metabolic syndrome
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DOI：
10.1016/j.atherosclerosis.2007.03.004
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发表时间：
2008-03-01
期刊：
影响因子：
5.3
通讯作者：
Watts, Gerald F.
中科院分区：
文献类型：
--
作者：
Ooi, Esther M. M.;Barrett, P. Hugh R.;Watts, Gerald F.
在一项随机、双盲、交叉试验中，安慰剂或瑞舒伐他汀（10 或 40 毫克/天）治疗 5 周，治疗之间使用 2 周安慰剂清除，研究了瑞舒伐他汀对代谢综合征受试者载脂蛋白 (apo) B-100 动力学的剂量依赖性影响。与安慰剂相比，瑞舒伐他汀治疗后血浆胆固醇、甘油三酯、LDL胆固醇、apoB和apoC-III浓度出现显着的剂量依赖性下降，并且apoB/apoA-I比值、拉索甾醇:胆固醇比值、HDL胆固醇浓度和菜油甾醇:胆固醇比值也显着增加。瑞舒伐他汀显着增加极低密度脂蛋白 (VLDL)、中密度脂蛋白 (IDL) 和 LDL-apoB 的分解代谢率 (FCR)，并减少相应的池大小，有证据表明存在剂量相关效应。瑞舒伐他汀 40 mg/天后，LDL apoB 生成率 (PR) 显着下降，而 VLDL 和 IDL-apoB PR 没有变化。甘油三酯的变化与 VLDL apoB FCR 和 apoC-III 浓度的变化显着相关，而 Lathosterol:cholesterol 比率的变化与 LDL apoB FCR 的变化相关，这种关联随着瑞舒伐他汀剂量的增加而更加显着。在代谢综合征中，瑞舒伐他汀通过剂量依赖性机制降低含 apoB 脂蛋白的血浆浓度，从而增加其分解代谢率。高剂量瑞舒伐他汀也可能减少 LDL apoB 的产生。这些发现为瑞舒伐他汀对代谢综合征心血管疾病的益处提供了剂量相关机制。 (c) 2007 年，爱思唯尔爱尔兰有限公司出版。
In a randomized, double-blind, crossovertrial of 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week placebo wash-outs between treatments, the dose-dependent effect of rosuvastatin on apolipoprotein (apo) B-100 kinetics in metabolic syndrome subjects were studied. Compared with placebo, there was a significant dose-dependent decrease with rosuvastatin in plasma cholesterol, triglycerides, LDL cholesterol, apoB and apoC-III concentrations and in the apoB/apoA-I ratio, lathosterol: cholesterol ratio, HDL cholesterol concentration and campesterol: cholesterol ratio also increased significantly. Rosuvastatin significantly increased the fractional catabolic rates (FCR) of very-low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and LDL-apoB and decreased the corresponding pool sizes, with evidence of a dose-related effect. LDL apoB production rate (PR) fell significantly with rosuvastatin 40 mg/day with no change in VLDL and IDL-apoB PR. Changes in triglycerides were significantly correlated with changes in VLDL apoB FCR and apoC-III concentration, and changes in lathosterol:cholesterol ratio were correlated with changes in LDL apoB FCR, the associations being more significant with the higher dose of rosuvastatin. In the metabolic syndrome, rosuvastatin decreases the plasma concentration of apoB-containing lipoproteins by a dose-dependent mechanism that increases their rates of catabolism. Higher dose rosuvastatin may also decrease LDL apoB production. The findings provide a dose-related mechanism for the benefits of rosuvastatin on cardiovascular disease in the metabolic syndrome. (c) 2007 Published by Elsevier Ireland Ltd.