INTERACTION OF LIPOPROTEIN LP(A) AND LOW-DENSITY LIPOPROTEIN WITH GLYCOSAMINOGLYCANS FROM HUMAN AORTA
INTERACTION OF LIPOPROTEIN LP(A) AND LOW-DENSITY LIPOPROTEIN WITH GLYCOSAMINOGLYCANS FROM HUMAN AORTA
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DOI：
10.1161/01.atv.8.6.851
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发表时间：
1988-11-01
期刊：
影响因子：
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通讯作者：
KOSTNER, GM
中科院分区：
文献类型：
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作者：
BIHARIVARGA, M;GRUBER, E;KOSTNER, GM
在Ca ~（++）存在下，用比浊法测定了从人胎盘中制备的糖胺聚糖（GAG）与脂蛋白Lp（a）和低密度脂蛋白（LDL）的脂蛋白络合活性。在对照实验中，使用纯化的硫酸软骨素-6和蛋白聚糖（PG）。Lp（a）表现出约三倍高的反应性。分析复合物的化学组成，我们发现Lp（a）对GAG的结合能力高出四倍以上。与LDL相比，Lp（a）与PG的结合能力高3.4倍。与GAG相比，两种脂蛋白对6-硫酸软骨素的结合能力仅为50%，但Lp（a）的反应性又高出4倍。LDL或Lp（a）的神经氨酸酶处理不干扰GAG或硫酸软骨素-6结合。另一方面，如果用二硫苏糖醇处理Lp（a），并去除Lp（a）特异性蛋白（载脂蛋白[apo]a），则GAG结合减少约45%。载脂蛋白a本身与GAG没有形成不溶性复合物。用小鼠腹腔巨噬细胞（MPM）孵育LDL和Lp（a）-sGAG和-LP（a）-PG复合物，研究其对胆固醇酯生成的刺激作用。在相同的脂蛋白胆固醇浓度下，Lp（a）-GAG复合物显示出比LDL-GAG高1.3倍的胆固醇酯化刺激。如果以摩尔为基础比较脂蛋白，这种差异就更加显著。PG-脂蛋白复合物与MPM的相互作用更加活跃。与MPM孵育后，发现PG-Lp（a）复合物中胆固醇酯形成量最高。由于游离GAG和PG存在于循环血液中，我们认为这可能有助于Lp（a）的高致动脉粥样硬化性。
The lipoprotein complexing activity of glycosaminoglycans (GAG) prepared from human aortas with lipoprotein Lp(a) in comparison to low density lipoproteins (LDL) was determined tubidimetrically in the presence of Ca++. In control experiments, purified chondroitin-6 sulfate and proteoglycans (PG) were used. Lp(a) exhibited approximately a threefold higher reactivity. Analyzing the chemical composition of the complexes, we found that Lp(a) had greater than fourfold higher binding capacity for GAG. The binding capacity of Lp(a) to PG was 3.4-fold higher as compared to LDL. The binding capacity of both lipoproteins for chondroitin-6 sulfate was only 50% in comparison to GAG, but again Lp(a) was four times more reactive. Neuraminidase treatment of LDL or Lp(a) did not interfere with GAG or chondroitin-6 sulfate binding. If, on the other hand, Lp(a) was treated with dithiothreitol and the Lp(a)-specific protein (apoprotein [apo]a) was revoved, the GAG binding was reduced by about 45%. Apo a by itself gave no insoluble complexes with GAG. LDL and Lp(a)-s GAG and -LP(a)-PG complexes were incubated with mouse peritoneal macrophages (MPM), and the stimulation of cholesteryl ester formation was studied. At identical lipoprotein cholesterol concentrations, Lp(a)-GAG complexes exhibited a 1.3-fold higher stimulation of cholesterol esterification as compared to LDL-GAG. This difference was even more striking if lipoproteins were compared at a molar basis. PG-lipoprotein complexes were much more active with respect to interactions with MPM. The highest amount of cholesterol ester formation upon incubation with MPM was found with PG-Lp(a) complexes. Since free GAGs, as well as PG, are present in circulating blood, we believe that this might contribute to the high atherogenicity of Lp(a).