LDL PHYSICAL AND CHEMICAL-PROPERTIES IN FAMILIAL COMBINED HYPERLIPIDEMIA
LDL PHYSICAL AND CHEMICAL-PROPERTIES IN FAMILIAL COMBINED HYPERLIPIDEMIA
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DOI：
10.1161/01.atv.15.4.452
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发表时间：
1995-04-01
影响因子：
8.7
通讯作者：
BRUNZELL, JD
中科院分区：
文献类型：
--
作者：
HOKANSON, JE;KRAUSS, RM;BRUNZELL, JD
家族性混合型高脂血症（FCHL）的特征是家族内甘油三酯和/或胆固醇升高以及apoB升高。尽管小而密LDL一直与高甘油三酯血症相关，但在FCHL患者中，尽管吉非罗齐治疗后甘油三酯降低，小而密LDL仍持续存在。本研究评估了FCHL患者和血脂正常对照组中LDL种类的分布和化学组成的潜在差异。来自FCHL患者的LDL的特征在于离散LDL种类的相对丰度，其平均峰值分析超离心浮选率（S-f（o））为4.7+/-0.5（SEM），密度为1.041+/-0.001 g/mL，并且通过梯度凝胶电泳评估的颗粒直径为250+/-1埃A。对照组受试者中的主要LDL种类具有较高的平均S-f（o）率（6.3+/-0.4），更具有浮力（密度，1.037+/-0.001 g/mL），并且更大（直径，262+/-2埃）。此外，在一系列的6个LDL组分分离的平衡密度梯度超离心，颗粒直径显着较小的FCHL患者与对照组相比，在所有馏分。患者的LDL颗粒中游离胆固醇、胆固醇酯和磷脂含量低于对照组。然而，FCHL患者和对照组之间每LDL颗粒的甘油三酯含量没有差异。患者和对照受试者之间主要LDL种类的漂浮率和质量的差异不能完全由血浆甘油三酯水平的差异来解释。因此，来自FCHL患者的LDL颗粒更小且更致密，具有更少的胆固醇和磷脂。许多这些差异似乎是独立的血浆甘油三酯。LDL物理和化学性质的差异可能有助于FCHL中早发冠心病的增加。
Familial combined hyperlipidemia (FCHL) is characterized by elevations of triglyceride and/or cholesterol within families and an elevation in apoB. Although small dense LDL has been consistently associated with hypertriglyceridemia, small dense LDL persists despite reductions in triglyceride after treatment with gemfibrozil in FCHL. The current study evaluated potential differences in the distribution and chemical composition of LDL species in patients with FCHL and normolipidemic control subjects. LDL from FCHL patients was characterized by a relative abundance of a discrete LDL species with a mean peak analytic ultracentrifuge flotation rate (S-f(o)) of 4.7+/-0.5 (SEM), a density of 1.041+/-0.001 g/mL, and a particle diameter of 250+/-1 Angstrom A as assessed by gradient gel electrophoresis. The major LDL species in the control subjects had a higher mean S-f(o) rate (6.3+/-0.4), was more buoyant (density, 1.037+/-0.001 g/mL), and was larger (diameter, 262+/-2 Angstrom). In addition, in a series of six LDL fractions separated by equilibrium density gradient ultracentrifugation, particle diameters were significantly smaller in all fractions from FCHL patients compared with those from control subjects. LDL particles from patients contained less free cholesterol, cholesteryl ester, and phospholipid than LDL from control subjects. The amount of triglyceride per LDL particle, however, did not differ between FCHL patients and control subjects. Differences in flotation rate and mass of the major LDL species between patients and control subjects could not be fully accounted for by differences in plasma triglyceride levels. Thus, LDL particles from FCHL patients are smaller and more dense with less cholesterol and phospholipid. Many of these differences appear to be independent of plasma triglyceride. Differences in LDL physical and chemical properties may contribute to the increase in premature coronary disease in FCHL.