Anber V, Millar J S, McConnell M, Shepherd J, Packard C J
University Department of Pathological Biochemistry, Glasgow Royal Infirmary, UK.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2507-14. doi: 10.1161/01.atv.17.11.2507.
The specific interaction of lipoproteins with arterial wall constituents, particularly proteoglycans (APG), is believed to play an important role in the development of atherosclerosis. The objective of this study was to examine the interaction of apolipoprotein B (apoB) containing lipoprotein subfractions (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; IDL1, Sf 16 to 20; IDL2, Sf 12 to 16; LDLA, Sf 8 to 12; and LDLB, Sf 0 to 8) prepared by cumulative density gradient centrifugation with chondroitin sulfate-rich APG. Eighteen subjects were studied, and a similar pattern of interaction between the lipoprotein species and APG was found in all. The order of reactivity (as measured by increased turbidity due to insoluble complex formation) was IDL Sf 12 to 16 > or = LDL Sf 8 to 12 > LDL Sf 0 to 8 > IDL Sf 16 to 20 >> VLDL Sf 20 to 60 > VLDL Sf 60 to 400. When the subjects were divided on the basis of their LDL subfraction profile, the extent of insoluble complex formation was highest in the group in which small, dense LDLIII was predominant; intermediate in the group whose LDL was mainly LDLII; and lowest in the group with a high proportion of LDLI (the mean reactivity, AU at 600 nm. of APG with IDL Sf 12 to 16 and LDL Sf 8 to 12 was 0.66; 0.62 and 0.46, 0.43 and 0.20, and 0.21 for the three groups, respectively). Fibrate lipid-lowering treatment decreased the percentage of LDLIII and increased the percentage of LDLI within total LDL and reduced the reactivity of all apoB-containing lipoprotein fractions toward APG. Sialic acid content varied in different lipoprotein subfractions, being the highest in VLDL and lowest in LDL. However, across lipoprotein species, it did not significantly correlate with APG-binding reactivity, suggesting that other factors are important in determining the interaction of lipoproteins with APG. Modification of LDL arginine and lysine residues abolished the ability of the lipoprotein to interact with APG, a finding that supports the hypothesis that the interaction is dependent on key positively charged amino acids on apoB. These findings demonstrate that (1) the overall reactivity of apoB-containing lipoproteins is greatest in individuals with small, dense LDL and (2) within an individual, IDL of Sf 12 to 16 is the most reactive species, and this may in part explain the positive correlation between IDL and risk of coronary heart disease.
脂蛋白与动脉壁成分，特别是蛋白聚糖（APG）的特异性相互作用，被认为在动脉粥样硬化的发展中起重要作用。本研究的目的是检测通过累积密度梯度离心法制备的含载脂蛋白B（apoB）的脂蛋白亚组分（极低密度脂蛋白1，Sf 60至400；极低密度脂蛋白2，Sf 20至60；中间密度脂蛋白1，Sf 16至20；中间密度脂蛋白2，Sf 12至16；低密度脂蛋白A，Sf 8至12；以及低密度脂蛋白B，Sf 0至8）与富含硫酸软骨素的APG之间的相互作用。对18名受试者进行了研究，发现所有受试者中脂蛋白种类与APG之间的相互作用模式相似。反应性顺序（通过因不溶性复合物形成导致的浊度增加来衡量）为：中间密度脂蛋白Sf 12至16≥低密度脂蛋白Sf 8至12＞低密度脂蛋白Sf 0至8＞中间密度脂蛋白Sf 16至20＞＞极低密度脂蛋白Sf 20至60＞极低密度脂蛋白Sf 60至400。当根据受试者的低密度脂蛋白亚组分谱进行分组时，不溶性复合物形成的程度在以小而密的低密度脂蛋白III为主的组中最高；在低密度脂蛋白主要为低密度脂蛋白II的组中居中；在低密度脂蛋白I比例高的组中最低（三组中，中间密度脂蛋白Sf 12至16和低密度脂蛋白Sf 8至12与APG在600nm处的平均反应性，吸光度单位分别为0.66；0.62、0.46、0.43、0.20和0.21）。贝特类降脂治疗降低了总低密度脂蛋白中低密度脂蛋白III的百分比，增加了低密度脂蛋白I的百分比，并降低了所有含apoB脂蛋白组分对APG的反应性。不同脂蛋白亚组分中的唾液酸含量不同，在极低密度脂蛋白中最高，在低密度脂蛋白中最低。然而，在不同脂蛋白种类中，它与APG结合反应性无显著相关性，这表明其他因素在决定脂蛋白与APG的相互作用中很重要。低密度脂蛋白精氨酸和赖氨酸残基的修饰消除了脂蛋白与APG相互作用的能力，这一发现支持了相互作用依赖于apoB上关键带正电荷氨基酸的假说。这些发现表明：（1）在小而密的低密度脂蛋白个体中，含apoB脂蛋白的总体反应性最大；（2）在个体内，Sf 12至16的中间密度脂蛋白是反应性最强的种类, 这可能部分解释了中间密度脂蛋白与冠心病风险之间的正相关。
