Animal model of autoimmune-induced atherosclerosis : Clinical significance of autoantibody against apolipoprotein A-I

自身免疫性动脉粥样硬化动物模型：载脂蛋白A-I自身抗体的临床意义

• 批准号: 08557133
• 负责人: UMEDA Masato
• 金额: $ 5.25万
• 依托单位: The Tokyo Metropolitan Institute of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557133/
• 关键词: apolipoprotein; atherosclerosis; high density lipoprotein; autoantibody; thrombosis; autoimmune disease; rheumatoid arthritis; cholesterol; アポリポタンパク質A-I; 血栓性疾患

Apolipoprotein A-I (apoA-I) is the major protein contituent of HDL, in which apoA-I plays an important role in extracellular lipid transport and metabolism. ApoA-I is an activator of lichithin-cholesterol acyltransferase, and several studies have indicated that apoA-I plays a role as a ligand capable of interacting with the cellular binding site for HDL.This study provides the first information about natural autoantibodies against apoA-I in normal individuals. We showed that the anti-apoA-I autoantibodies bound effectively to oxidized HDL and also to apoA-I complexed with oxidized lipids. The epitope for the anti-apoA-I autoantibody was localized to N-terminus end of apoA-I, suggesting that the lipid peroxidation of HDL may cause a conformational change of apoA-I, resulting in the exposure of the N-terminal autologous antigenic site for the autoantibodies against apoA-I.We also found that serum level of anti-apoA-I autoantibody was reversely correlated with the serum concentration of HDL, implying the autoantibody plays a role in clearance of oxidixed HDL.Immunoglobulin gene sequences of the autoantibodies were also determined.

载脂蛋白A-I（apoA-I）是高密度脂蛋白（HDL）的主要组成蛋白，在细胞外脂质转运和代谢中起重要作用。ApoA-I是地衣素-胆固醇酰基转移酶的激活剂，研究表明apoA-I作为配体与HDL的细胞结合位点相互作用，本研究首次提供了正常人抗apoA-I自身抗体的信息。我们表明，抗apoA-I自身抗体有效地结合氧化HDL，也与apoA-I复合氧化脂质。抗apoA-I自身抗体的抗原表位位于apoA-I的N端，提示HDL的脂质过氧化作用可能引起apoA-I的构象变化，使apoA-I自身抗体的N端抗原位点暴露。提示该自身抗体在清除氧化HDL中起一定作用，并测定了其免疫球蛋白基因序列。

项目成果

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F.Lan et al.: "Extended fitmess of variable region primers by a novel PCR protocol." J.Immunol.Methods. 195. 27-32 (1996)

F.Lan 等人：“通过新颖的 PCR 方案扩展了可变区引物的适应性。”