Immune response to lysine adducts in atherogenesis

2018 Fiscal Year Final Research Report

• 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
• Keywords: 酸化ストレス / 動脈硬化 / リジン付加体

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.

Free Research Field

酸化ストレスと疾病

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。