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家族性混合性高脂血症中的低密度脂蛋白颗粒大小:血清脂质、脂蛋白修饰酶和脂质转运蛋白的影响

LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins.

作者信息

Vakkilainen Juha, Jauhiainen Matti, Ylitalo Kati, Nuotio Ilpo O, Viikari Jorma S A, Ehnholm Christian, Taskinen Marja-Riitta

机构信息

Department of Medicine, Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 340, 00029 HUCH, Helsinki, Finland.

出版信息

J Lipid Res. 2002 Apr;43(4):598-603.

PMID:11907142
Abstract

Small, dense LDL particles are typical for FCHL. Intravascular lipid exchange and net transfer among HDL, LDL, and triglyceride-rich lipoproteins as well as lipolysis in the VLDL-IDL-LDL cascade regulate properties of LDL. We investigated postheparin plasma activities of hepatic lipase (HL) and LPL, and plasma activities of CETP and phospholipid transfer protein (PLTP) in 191 individuals from 37 Finnish FCHL families. LDL peak particle diameter (LDL size) was measured with 2-10% gradient polyacrylamide gel electrophoresis. LDL size was significantly smaller in affected FCHL family members (n = 68) as compared with nonaffected FCHL family members (n = 78) or spouses (n = 45) (25.3 +/- 1.5 nm, 26.8 +/- 1.2 nm, and 26.6 +/- 1.2 nm, respectively, P < 0.001 for both). In affected FCHL family members, serum triglycerides were the strongest correlate for LDL size (r = -0.71, P < 0.001). In univariate correlation analysis LDL size was not associated with HL, LPL, CETP, and PLTP activities. In multivariate stepwise regression analysis, however, serum triglycerides, CETP activity, HL activity, and HDL cholesterol were significant predictors of LDL size in affected FCHL subjects (adjusted r (2) = 0.642). We conclude that serum triglyceride concentration is strongly correlated with LDL size in affected FCHL subjects. After adjustment for serum triglycerides, HL and CETP activities are associated with LDL size in FCHL.

摘要

小而致密的低密度脂蛋白颗粒是家族性混合型高脂血症(FCHL)的典型特征。高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和富含甘油三酯的脂蛋白之间的血管内脂质交换及净转运,以及极低密度脂蛋白(VLDL)-中间密度脂蛋白(IDL)-低密度脂蛋白级联反应中的脂解作用,调节着低密度脂蛋白的特性。我们对来自37个芬兰FCHL家族的191名个体,研究了肝素后血浆中肝脂酶(HL)和脂蛋白脂肪酶(LPL)的活性,以及胆固醇酯转运蛋白(CETP)和磷脂转运蛋白(PLTP)的血浆活性。用2%-10%梯度聚丙烯酰胺凝胶电泳测定LDL峰值颗粒直径(LDL大小)。与未受影响的FCHL家族成员(n = 78)或配偶(n = 45)相比,受影响的FCHL家族成员(n = 68)的LDL大小明显更小(分别为25.3±1.5nm、26.8±1.2nm和26.6±1.2nm,两者比较P均<0.001)。在受影响的FCHL家族成员中,血清甘油三酯与LDL大小的相关性最强(r = -0.71,P < 0.001)。在单变量相关性分析中,LDL大小与HL、LPL、CETP和PLTP活性无关。然而,在多变量逐步回归分析中,血清甘油三酯、CETP活性、HL活性和HDL胆固醇是受影响的FCHL受试者LDL大小的显著预测因素(调整后r² = 0.642)。我们得出结论,在受影响的FCHL受试者中,血清甘油三酯浓度与LDL大小密切相关。在调整血清甘油三酯后,HL和CETP活性与FCHL中的LDL大小相关。

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