Tertov V V, Sobenin I A, Orekhov A N, Jaakkola O, Solakivi T, Nikkari T
Institute of Experimental Cardiology, Cardiology Research Center, Moscow, Russian Federation.
Atherosclerosis. 1996 May;122(2):191-9. doi: 10.1016/0021-9150(95)05737-4.
Circulating immune complexes (CIC) containing low density lipoprotein (LDL) were recently found in the blood of patients with coronary atherosclerosis. In the present study, we investigated the chemical composition and physical characteristics of the lipoprotein constituents of these CIC. CIC were isolated from the blood of atherosclerotic patients by affinity chromatography using anti-human immunoglobulin G-agarose. Low density lipoprotein of these complexes (CIC-LDL) was obtained by ultracentrifugation. CIC-LDL was compared with free circulating LDL isolated from the blood plasma of the same patients. Plasma LDL was fractionated by lectin-chromatography on RCA120-agarose to obtain desialylated LDL (atherogenic) and sialylated LDL (nonatherogenic). Both CIC-LDL and desialylated LDL, but not native (sialylated) lipoprotein, induced a 1.8- to 3-fold increase in the intracellular contents of free and esterified cholesterol of cells cultured from grossly normal areas of human aorta. The sialic acid level in CIC-LDL was 1.3- and 2.1-fold lower than in desialylated or native LDL, respectively. The neutral lipid and phospholipid contents of CIC-LDL and desialylated LDL were reduced as compared to native LDL. The levels of lipid-oxidation products, thiobarbituric acid-reactive substances and hydroperoxides, were similar in all lipoprotein preparations. However, desialylated LDL and CIC-LDL had an elevated oxysterol content. Gradient ultracentrifugation revealed that CIC-LDL particles had a higher density than native LDL. The mean diameters of native, desialylated and CIC-LDL accounted for 24.0, 21.3 and 19.5 nm, respectively. Like desialylated LDL, CIC-LDL displayed a higher electrophoretic mobility compared with that of native LDL. Thus, LDL obtained from circulating immune complexes appears to be a multiple-modified lipoprotein possessing many similarities to desialylated LDL. It was also found that the LDL content of circulating immune complexes correlates well with the desialylated LDL level in human plasma but not with the total LDL concentration. We believe that desialylated LDL predominately interacts with antibodies forming immune complexes. Taken together, our findings suggest that multiple-modified desialylated LDL is the circulating autoantigen for anti-LDL autoantibodies.
最近在冠状动脉粥样硬化患者的血液中发现了含有低密度脂蛋白（LDL）的循环免疫复合物（CIC）。在本研究中，我们调查了这些CIC中脂蛋白成分的化学组成和物理特性。通过使用抗人免疫球蛋白G-琼脂糖的亲和色谱法从动脉粥样硬化患者的血液中分离出CIC。通过超速离心获得这些复合物的低密度脂蛋白（CIC-LDL）。将CIC-LDL与从同一患者血浆中分离出的游离循环LDL进行比较。通过在RCA120-琼脂糖上进行凝集素色谱法对血浆LDL进行分级分离，以获得去唾液酸LDL（致动脉粥样硬化）和唾液酸化LDL（非致动脉粥样硬化）。CIC-LDL和去唾液酸LDL，但不是天然（唾液酸化）脂蛋白，均使从人主动脉大体正常区域培养的细胞内游离胆固醇和酯化胆固醇含量增加了1.8至3倍。CIC-LDL中的唾液酸水平分别比去唾液酸LDL或天然LDL低1.3倍和2.1倍。与天然LDL相比，CIC-LDL和去唾液酸LDL的中性脂质和磷脂含量降低。所有脂蛋白制剂中脂质氧化产物、硫代巴比妥酸反应性物质和氢过氧化物的水平相似。然而，去唾液酸LDL和CIC-LDL的氧化甾醇含量升高。梯度超速离心显示CIC-LDL颗粒的密度高于天然LDL。天然、去唾液酸和CIC-LDL的平均直径分别为24.0、21.3和19.5nm。与天然LDL相比，CIC-LDL和去唾液酸LDL一样，显示出更高的电泳迁移率。因此，从循环免疫复合物中获得的LDL似乎是一种多重修饰的脂蛋白，与去唾液酸LDL有许多相似之处。还发现循环免疫复合物中的LDL含量与人类血浆中的去唾液酸LDL水平密切相关，但与总LDL浓度无关。我们认为去唾液酸LDL主要与抗体相互作用形成免疫复合物。综上所述，我们的研究结果表明多重修饰的去唾液酸LDL是抗LDL自身抗体的循环自身抗原。
