1998 Fiscal Year Final Research Report Summary
Animal model of autoimmune-induced atherosclerosis : Clinical significance of autoantibody against apolipoprotein A-I
| Project/Area Number |
08557133
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | The Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
UMEDA Masato The Tokyo Metropolitan Institute of Medical Science, Department of Molecular Biodynamics, 炎症研究部門, 研究員 (10185069)
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| Co-Investigator(Kenkyū-buntansha) |
五十嵐 浩二 東ソー株式会社, 生理工学研究所, 研究員
KANAI Noboru Tosoh Corporation, Tokyo Research Center, 生理工学研究所, 所長
ARAI Morio Tokyo Medical College, Department of Clinical Pathology, 臨床病理学教室, 助教授 (00212605)
YONEKAWA Hiromichi The Tokyo Metropolitan Institute of Medical Science, Department of Laboratory An, 実験動物研究部門, 研究員 (30142110)
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| Project Period (FY) |
1996 – 1998
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| Keywords | apolipoprotein / atherosclerosis / high density lipoprotein / autoantibody / thrombosis / autoimmune disease / rheumatoid arthritis / cholesterol |
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| Research Abstract |
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.
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