Tertov V V, Sobenin I A, Gabbasov Z A, Popov E G, Jaakkola O, Solakivi T, Nikkari T, Smirnov V N, Orekhov A N
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russia.
Lab Invest. 1992 Nov;67(5):665-75.
The basic differences between sialylated (sialic acid rich) and desialylated (sialic acid poor) human low density lipoproteins (LDL) are not fully defined. It is not known whether there are any differences in the LDL composition of coronary atherosclerosis patients and healthy individuals.
Sialylated (45 to 94% of total LDL) and desialylated (6 to 55%) LDL were separated by affinity chromatography on Ricinus communis agglutinin-agarose, and their chemical composition and physical properties were examined.
Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were the same and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated ones. Desialylated, but not sialylated LDL, induced 1.5- to 4-fold accumulation of neutral lipids in human aortic smooth muscle cells and human blood monocytes. Subfractions of desialylated LDL containing lower amount of sialic acid revealed higher ability to accumulate lipids in cultured cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared with sialylated LDL. On the other hand, concentration of di-, monoglycerides and free fatty acids in desialylated LDL was 2 to 3-fold higher than in sialylated lipoproteins. Desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, but higher content of lysophosphatidylcholine. Freshly isolated sialylated and desialylated LDL contained equal amounts of thiobarbituric acid reactive substances, but oxidation of desialylated LDL was more pronounced in presence of Cu(2+)-ions. Desialylated LDL had higher level of oxysterols and lower amounts of vitamin A and E. Content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. This difference was partially due to masking of amino groups caused by conformational change in the tertiary structure of apolipoprotein, partially to chemical modification of amino groups. When subfractionated by density gradient ultracentrifugation, desialylated LDL was represented by higher density particles than sialylated LDL. Sialic acid content in desialylated LDL subfractions decreased with rise of lipoprotein density. Higher density desialylated LDL and in less extent sialylated LDL contained smaller amounts of free and esterified cholesterol and phospholipids. Only the densest subfractions of desialylated LDL from healthy subjects caused intracellular lipid accumulation. Ability of patients' desialylated LDL to accumulate cholesterol in cells increased with particle density.
Extensive biochemical and biophysical analysis performed in this study shows that desialylated LDL differ from these sialylated LDL in many respects. The LDL of coronary atherosclerosis patients differ from those in healthy individuals in several parameters.
富含唾液酸的（唾液酸丰富的）和去唾液酸化的（唾液酸缺乏的）人低密度脂蛋白（LDL）之间的基本差异尚未完全明确。目前尚不清楚冠状动脉粥样硬化患者和健康个体的LDL组成是否存在差异。
通过蓖麻凝集素 - 琼脂糖亲和色谱法分离唾液酸化的（占总LDL的45%至94%）和去唾液酸化的（占6%至55%）LDL，并检测其化学组成和物理性质。
健康受试者和患者的唾液酸化LDL组分中的唾液酸含量相同，且比去唾液酸化LDL高1.5至3倍。去唾液酸化LDL的尺寸比唾液酸化LDL小，电泳迁移率更高。去唾液酸化而非唾液酸化的LDL可诱导人主动脉平滑肌细胞和人血单核细胞中中性脂质积累1.5至4倍。唾液酸含量较低的去唾液酸化LDL亚组分在培养细胞中积累脂质的能力更高。与唾液酸化LDL相比，去唾液酸化LDL含有的胆固醇酯、游离胆固醇和甘油三酯含量较低。另一方面，去唾液酸化LDL中二酰甘油、单酰甘油和游离脂肪酸的浓度比唾液酸化脂蛋白高2至3倍。去唾液酸化LDL组分的特征是磷脂酰胆碱、鞘磷脂、磷脂酰乙醇胺水平较低，但溶血磷脂酰胆碱含量较高。新鲜分离的唾液酸化和去唾液酸化LDL含有等量的硫代巴比妥酸反应性物质，但在铜离子存在下，去唾液酸化LDL的氧化更为明显。去唾液酸化LDL的氧化甾醇水平较高，维生素A和E含量较低。患者去唾液酸化LDL中赖氨酸的游离氨基含量比唾液酸化LDL低2倍。这种差异部分是由于载脂蛋白三级结构的构象变化导致氨基被掩盖，部分是由于氨基的化学修饰。当通过密度梯度超速离心进行亚分级时，去唾液酸化LDL比唾液酸化LDL以更高密度的颗粒形式存在。去唾液酸化LDL亚组分中的唾液酸含量随脂蛋白密度升高而降低。更高密度的去唾液酸化LDL以及程度较小的唾液酸化LDL含有较少的游离和酯化胆固醇及磷脂。只有来自健康受试者的最致密的去唾液酸化LDL亚组分引起细胞内脂质积累。患者去唾液酸化LDL在细胞中积累胆固醇的能力随颗粒密度增加而增强。
本研究进行的广泛生化和生物物理分析表明，去唾液酸化LDL在许多方面与唾液酸化LDL不同。冠状动脉粥样硬化患者的LDL在几个参数上与健康个体的LDL不同。
