Millar J S, Anber V, Shepherd J, Packard C J
Department of Pathological Biochemistry, Glasgow Royal Infirmary, Scotland, UK.
Atherosclerosis. 1999 Aug;145(2):253-60. doi: 10.1016/s0021-9150(99)00071-4.
Sialic acid is a negatively charged sugar associated with the protein and lipid portions of lipoproteins. Sialic acid has been hypothesised to play an anti-atherogenic role in lipoprotein metabolism through the electrostatic inhibition of lipoprotein interactions with chondroitin-6-sulphate-rich arterial proteoglycans (APG). We conducted a series of studies using native and modified lipoproteins (VLDL1 Sf 60-400, VLDL2 Sf 20-60, IDL1 Sf 16-20, IDL2 Sf 12-16, LDL(A) Sf 8-12, and LDL(B) Sf0-8) that vary in their sialic acid content to examine the relationship between lipoprotein sialic acid content and its interaction with APG. Lipoprotein sialic acid was greatest in VLDL1 and decreased progressively with particle density until the IDL2 fraction (VLDL1 > VLDL2 > IDL1 > IDL2 = LDL(A) = LDL(B)). The pattern of reactivity of each fraction with APG was different from the pattern observed for lipoprotein sialic acid content (IDL2 > LDL(A) > LDL(B) > IDL1 > VLDL2 > VLDL1). Levels of sialic acid were lower in subjects with CHD as compared to control subjects but the presence of CHD had no effect on lipoprotein-APG complex formation when sex and plasma triglyceride levels were taken into account. There was also no significant relationship between the lipoprotein sialic acid content and the reactivity with APG within each lipoprotein fraction. Treatment of hypertriglyceridaemic subjects with ciprofibrate decreased lipoprotein-APG complex formation in all lipoprotein fractions. This was associated with a decrease in the total sialic acid content of apo B100-containing lipoproteins suggesting that the total sialic acid content of apo B100-containing lipoproteins has no influence on lipoprotein-APG complex formation. We next conducted in vitro experiments to manipulate LDL sialic acid content. Enzymatic removal of sialic acid from LDL with neuraminidase resulted in an increase in LDL-APG complex formation. This was accompanied by an increase in the exposure of free amino groups on LDL possibly due to disruption of interactions between free amino groups and sialic acid-containing components on LDL. Increasing LDL sialic acid content through incubation with ganglioside resulted in a decrease in lipoprotein-APG complex formation without any changes in the exposure of free amino groups on LDL. We conclude that total sialic acid content of lipoproteins is not a major determinant of their binding to APG. However, specific sialic acid-containing components on lipoproteins can affect their interaction with APG.
唾液酸是一种带负电荷的糖，与脂蛋白的蛋白质和脂质部分相关联。有人提出，唾液酸通过静电抑制脂蛋白与富含硫酸软骨素 - 6 - 硫酸酯的动脉蛋白聚糖（APG）的相互作用，在脂蛋白代谢中发挥抗动脉粥样硬化作用。我们使用了天然和修饰的脂蛋白（VLDL1 Sf 60 - 400、VLDL2 Sf 20 - 60、IDL1 Sf 16 - 20、IDL2 Sf 12 - 16、LDL(A) Sf 8 - 12和LDL(B) Sf0 - 8）进行了一系列研究，这些脂蛋白的唾液酸含量各不相同，以研究脂蛋白唾液酸含量与其与APG相互作用之间的关系。VLDL1中的脂蛋白唾液酸含量最高，随着颗粒密度的增加逐渐降低，直至IDL2部分（VLDL1 > VLDL2 > IDL1 > IDL2 = LDL(A) = LDL(B)）。每个部分与APG的反应模式与脂蛋白唾液酸含量观察到的模式不同（IDL2 > LDL(A) > LDL(B) > IDL1 > VLDL2 > VLDL1）。与对照组相比，冠心病患者的唾液酸水平较低，但在考虑性别和血浆甘油三酯水平时，冠心病的存在对脂蛋白 - APG复合物的形成没有影响。在每个脂蛋白部分中，脂蛋白唾液酸含量与与APG的反应性之间也没有显著关系。用环丙贝特治疗高甘油三酯血症患者可降低所有脂蛋白部分中脂蛋白 - APG复合物的形成。这与含载脂蛋白B100的脂蛋白总唾液酸含量的降低有关，表明含载脂蛋白B100的脂蛋白总唾液酸含量对脂蛋白 - APG复合物的形成没有影响。接下来，我们进行了体外实验来操纵低密度脂蛋白（LDL）的唾液酸含量。用神经氨酸酶从LDL中酶促去除唾液酸导致LDL - APG复合物形成增加。这可能伴随着LDL上游离氨基暴露的增加，这可能是由于游离氨基与LDL上含唾液酸成分之间的相互作用被破坏所致。通过与神经节苷脂孵育增加LDL唾液酸含量导致脂蛋白 - APG复合物形成减少，而LDL上游离氨基的暴露没有任何变化。我们得出结论，脂蛋白的总唾液酸含量不是其与APG结合的主要决定因素。然而，脂蛋白上特定的含唾液酸成分可以影响它们与APG的相互作用。
