Skoglund-Andersson C, Tang R, Bond M G, de Faire U, Hamsten A, Karpe F
Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2422-30. doi: 10.1161/01.atv.19.10.2422.
Results of cross-sectional and prospective studies have suggested that small, dense low-density lipoprotein (LDL) particles predispose to coronary heart disease. We investigated the relationships between plasma concentrations of LDL subfractions and intima-media thickness (IMT) of the common carotid artery (CCA), quantified by B-mode ultrasound, in 94 healthy, 50-year-old men, all of whom were homozygous for the apolipoprotein E3 allele. A novel 3% to 7.5% polyacrylamide gradient gel was developed to provide separation of LDL subfractions with high resolution, as was a procedure to quantify plasma concentrations of these LDL subspecies. The LDL particle size distribution pattern obtained by the gradient gel electrophoresis procedure was in good agreement with the one obtained by a well-established, single-spin density gradient ultracentrifugation technique. LDL-II (particle size, 23.5 to 25.0 nm) was the most abundant subfraction, and its plasma concentration correlated closely with the total LDL cholesterol concentration (r=0. 61, P<0.001) but not with CCA IMT (r=-0.13, NS). In contrast, the plasma concentration of the predominant small, dense LDL particle subfraction (LDL-III; particle size, 22.5 to 23.5 nm) correlated strongly with CCA IMT (r=0.42, P<0.001). In multivariate analysis, the plasma concentration of the LDL-III subfraction contributed significantly to the variation in CCA IMT (R(2)=0.19). When plasma triglycerides and LDL cholesterol were forced into the multivariate model, 10% of the variation in CCA IMT was still accounted for by the LDL-III subfraction. In summary, use of a novel and sensitive gradient gel electrophoresis method for evaluation of LDL heterogeneity provided the basis for demonstrating an independent relation between the plasma concentration of small LDL and IMT of the CCA in healthy, middle-aged men.
横断面研究和前瞻性研究结果表明，小而致密的低密度脂蛋白（LDL）颗粒易引发冠心病。我们在94名健康的50岁男性中，研究了LDL亚组分的血浆浓度与通过B型超声定量的颈总动脉（CCA）内膜中层厚度（IMT）之间的关系，所有这些男性均为载脂蛋白E3等位基因的纯合子。开发了一种新型的3%至7.5%聚丙烯酰胺梯度凝胶，以实现LDL亚组分的高分辨率分离，同时还开发了一种定量这些LDL亚类血浆浓度的方法。通过梯度凝胶电泳程序获得的LDL颗粒大小分布模式与通过成熟的单旋密度梯度超速离心技术获得的模式高度一致。LDL-II（颗粒大小为23.5至25.0 nm）是最丰富的亚组分，其血浆浓度与总LDL胆固醇浓度密切相关（r = 0.61，P < 0.001），但与CCA IMT无关（r = -0.13，无显著性差异）。相比之下，主要的小而致密的LDL颗粒亚组分（LDL-III；颗粒大小为22.5至23.5 nm）的血浆浓度与CCA IMT密切相关（r = 0.42，P < 0.001）。在多变量分析中，LDL-III亚组分的血浆浓度对CCA IMT的变化有显著贡献（R(2)=0.19）。当将血浆甘油三酯和LDL胆固醇纳入多变量模型时，LDL-III亚组分仍可解释CCA IMT变化的10%。总之，使用新型灵敏的梯度凝胶电泳方法评估LDL异质性，为证明健康中年男性中小LDL的血浆浓度与CCA IMT之间的独立关系提供了依据。
