Establishment of Molecular Imaging and Lipidomics Technologies for Early Diagnosis of Atherosclerotic Disease

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253036
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Okayama University
• Principal Investigator: MATSUURA Eiji 岡山大学, 医歯薬学総合研究科, 教授 (20181688)
• Co-Investigator(Kenkyū-buntansha): 保田 晋助 北海道大学, 医学(系)研究科(研究院), 講師 (00374231)
• Co-Investigator(Renkei-kenkyūsha): SASAKI Takanori 岡山大学, 医歯(薬)学総合研究科, 助教 (10461253) ; KOBAYASHI Kazuko 岡山大学, 医歯(薬)学総合研究科, 助教 (20304298) ; TAKENAKA Fumiaki 岡山大学, 医歯(薬)学総合研究科, 助教 (10642522) ; OZEKI Eiichi (株)島津製作, 基盤技術研究所, 研究員 (30192529) ; FUJIWAKE Hideshi (株)島津製作所, 分析計測事業部, 研究者 (50395696) ; KOBUCHI Hirotsugu 岡山大学, 医歯(薬)学総合研究科, 講師 (10304297)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 動脈硬化 / Beta2-glycoprotein I / 血栓・止血 / 血管新生 / 抗リン脂質抗体症候群 / メタボロミクス / リピドミクス / LC-MS/MS

Outline of Final Research Achievements

B2-Glycoprotein I (B2GPI) is a multifunctional plasma protein consisting of five homologous domains that control thrombosis/hemostasis and angiogenesis. Its physiological activity and binding affinity to particular phospholipids, oxidized lipids and/or proteins are regulated by the enzymatic activity of plasmin. In the present study, we identified a novel cleavage site by plasmin and produced plasmin-resistant recombinant proteins of domain V and domain I. With these, we have confirmed their localization at angiogenic legions in mouse xenograft models via PET imaging, and their respective physiological functions in vitro and in vivo. In addition, a metabolomic-based approach involving the combination of B2GPI-affinity column and LC-MS/MS has also been constructed to comprehensively analyse oxidized lipids involved in the development of atherosclerotic diseases.

Free Research Field

病態検査学