Immune response to lysine adducts in atherogenesis

Research Project

Project/Area Number	17H07027
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Metabolomics
Research Institution	Osaka Prefecture University
Principal Investigator	Nakamura Jun 大阪府立大学, 生命環境科学研究科, 客員研究員 (90804518)
Project Period (FY)	2017-08-25 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	酸化ストレス / 動脈硬化 / リジン付加体 / 粥状動脈硬化 / ApoE欠損マウス / ApoEノックアウトマウス / 循環器・高血圧
Outline of Final Research Achievements	It has been shown that 1,4-dihydropyridine-type malondialdehyde (MDA)- Acetaldehyde (AA)-lysine (M2AA) adducts are formed during atherogenesis. Previously, we detected an increase in antibody against M2AA in the blood in atherosclerosis-prone ApoE ko mice. We hypothesized that the combination of AA, MDA, and lysine could lead to the formation of additional immunogenic adducts other than M2AA. In the present study, the reaction product of AA, MDA, and 6-aminocaproic acid (6-ACA, a lysine analog) was fractionated by HPLC. Interestingly, we found that the titers of antibodies against all of the fractionated products were increased in the blood of ApoE ko mice, indicating the existence of multiple immunogenic epitopes in the reactant of MDA, FA, and 6ACA. From this, we believe that evaluating serum titers of natural antibodies against various complex MDA-AA-lysine adducts could be used as a biomarker for metabolic syndromes.
Academic Significance and Societal Importance of the Research Achievements	生活習慣病に罹患している患者が増加する中で疾病の進展をモニターできるバイオマーカーの確立が求められている。リジン付加体の一つであるM2AAは免疫原性があり、非常に安定な付加体であり、粥状動脈硬化症や非アルコール性肝炎の新しいバイオマーカーとして期待されている。本研究からM2AA以外にもこれら生活習慣病のバイオマーカーとなりうるリジン付加体が存在しうることが明らかになった。