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脂蛋白脂肪酶缺乏症及其他原发性高甘油三酯血症中的胆固醇酯转移活性。

Cholesteryl ester transfer activity in lipoprotein lipase deficiency and other primary hypertriglyceridemias.

作者信息

Iglesias A, Contreras J A, Martínez-Pardo M, Entrala A, Herrera E, Lasunción M A

机构信息

Service of Bioquímica-Investigación, Hospital Ramón y Cajal, Madrid, Spain.

出版信息

Clin Chim Acta. 1993 Nov 30;221(1-2):73-89. doi: 10.1016/0009-8981(93)90023-w.

DOI:10.1016/0009-8981(93)90023-w
PMID:8149644
Abstract

Cholesteryl ester transfer protein (CETP) activity was measured in d > 1.21 g/ml plasma from hypertriglyceridemic patients and compared with normolipidemic subjects. The assay consisted in measuring the specific transfer of [3H]cholesteryl oleate from a prelabelled, apo E-poor HDL fraction to VLDL after incubation at 37 degrees C in the presence of the d > 1.21 g/ml plasma sample: the lipoproteins were then separated by precipitation with dextran sulfate/Mg2+ solution. Increasing the volume of d > 1.21 g/ml plasma or purified human CETP in the assay produced linear responses in measured activity, whereas, either during incubation at 4 degrees C or in the presence of rat plasma instead of human plasma, the transfer of [3H]cholesteryl oleate to VLDL was not stimulated. Thus, the assay reflects changes in CETP in the sample and appears to be suitable for measuring CETP activity in d > 1.21 g/ml plasma. CETP activity was very similar in the two groups of normolipidemic subjects considered: adolescents (203 +/- 11 nmol esterified cholesterol transferred per 8 h/ml plasma) and adults (215 +/- 5). Patients were grouped into lipoprotein-lipase (LPL)-deficient and non-LPL-deficient according to their enzyme activity in postheparin plasma. CETP activity was highly increased in LPL-deficient, severe hyperchylomicronemic patients (430 +/- 42) and was directly correlated with VLDL levels in the non-LPL-deficient individuals. Marked differences were observed in the lipid composition of HDL and apolipoprotein A-I levels among patients and controls. In the control group, CETP activity was correlated only with HDL-triglyceride and HDL-triglyceride/apo A-I mass ratio, which is compatible with the physiological role of CETP in transferring triglyceride to HDL from other lipoprotein particles. When all hypertriglyceridemic patients were considered together, CETP activity was inversely correlated with apo A-I and HDL-cholesterol, whereas it was directly correlated with HDL-triglyceride/HDL-cholesterol and HDL-triglyceride/apo A-I mass ratios. The results indicate that the enhanced CETP activity associated with hypertriglyceridemia contributes to the compositional change of HDL, which in turn may be responsible for the reduction of HDL levels in this condition.

摘要

在高甘油三酯血症患者密度大于1.21 g/ml的血浆中测量胆固醇酯转移蛋白(CETP)活性,并与血脂正常的受试者进行比较。该检测方法包括在37℃下,在存在密度大于1.21 g/ml血浆样本的情况下,测量[3H]油酸胆固醇从预先标记的、载脂蛋白E含量低的高密度脂蛋白(HDL)组分向极低密度脂蛋白(VLDL)的特异性转移:然后用硫酸葡聚糖/Mg2+溶液沉淀分离脂蛋白。在检测中增加密度大于1.21 g/ml血浆或纯化的人CETP的体积,在测量的活性中产生线性反应,而在4℃孵育期间或存在大鼠血浆而非人血浆时,[3H]油酸胆固醇向VLDL的转移未受到刺激。因此,该检测反映了样本中CETP的变化,似乎适用于测量密度大于1.??21 g/ml血浆中的CETP活性。在所考虑的两组血脂正常的受试者中,CETP活性非常相似:青少年(每8小时/毫升血浆转移203±11 nmol酯化胆固醇)和成年人(215±5)。根据肝素后血浆中的酶活性,将患者分为脂蛋白脂肪酶(LPL)缺乏和非LPL缺乏组。LPL缺乏的严重高乳糜微粒血症患者的CETP活性显著升高(430±42),并且在非LPL缺乏个体中与VLDL水平直接相关。在患者和对照组之间,观察到HDL的脂质组成和载脂蛋白A-I水平存在明显差异。在对照组中,CETP活性仅与HDL-甘油三酯以及HDL-甘油三酯/载脂蛋白A-I质量比相关,这与CETP将甘油三酯从其他脂蛋白颗粒转移到HDL中的生理作用相符。当将所有高甘油三酯血症患者一起考虑时,CETP活性与载脂蛋白A-I和HDL-胆固醇呈负相关,而与HDL-甘油三酯/HDL-胆固醇以及HDL-甘油三酯/载脂蛋白A-I质量比呈正相关。结果表明,与高甘油三酯血症相关的CETP活性增强导致了HDL的组成变化,这反过来可能是导致这种情况下HDL水平降低的原因。

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