Development of diagnostic method for atherosclerosis based on adipokine regulatory factors

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02731
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Osaka University
• Principal Investigator: Kihara Shinji 大阪大学, 医学系研究科, 教授 (20332736)
• Co-Investigator(Kenkyū-buntansha): 山本 浩靖 大阪大学, 医学系研究科, 准教授 (00631201)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 蛋白質 / 生体分子 / 分析科学 / 細胞・組織 / 医療・福祉

Outline of Final Research Achievements

Based on the combination of immunoprecipitation and mass spectrometry analysis of human serum and cultured human cells, we identified C-C motif chemokine 2 (CCL2) and Frizzled (FZD) as novel adiponectin binding proteins.
We found that the percentage of plaque in the coronary culprit lesions was negatively correlated with serum adiponectin levels and positively correlated with serum CCL2 levels, with significance, in male patients with stable angina. The anti-atherogenic property of adiponectin-CCL2 binding was functionally demonstrated by the inhibition of monocyte migration and MAP kinase phosphorylation, and these mechanisms could explain the clinical findings.　 In addition, we speculated that adiponectin can compete Wnt-mediated pro-atherogenic signals through the direct binding of FZD.

Free Research Field

臨床検査医学

Academic Significance and Societal Importance of the Research Achievements

アディポネクチン結合蛋白として新たにC-C motif chemokine 2 （CCL2）を見出し、狭心症患者において血中CCL2濃度が冠動脈狭窄の程度と有意に相関することを報告した。
CCL2は単球を血管に遊走させ動脈硬化を進展させる作用を持つ分子であり、この遊走促進作用をアディポネクチンが阻害するという、新しい動脈硬化抑制機序を明らかにした。
またアディポネクチン結合蛋白としてFrizzled （FZD）も見出し、アディポネクチンはFZD と結合することでも動脈硬化を抑制することが推察された。