The role of Syk in molecular mechanism of abdominal aortic aneurysm

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K16406
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Kurume University
• Principal Investigator: Kanamoto Ryo 久留米大学, 医学部, 助教 (70817353)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: Syk / 腹部大動脈瘤 / B細胞 / 免疫グロブリン

Outline of Final Research Achievements

In this study, we aimed to investigate the role of Syk in human abdominal aortic aneurysm (AAA) pathogenesis using human AAA tissue. Immunohistochemical analysis showed infiltration of B cells, T cells, and macrophages in AAA samples. Syk activation was localized mainly in B cells and part of macrophages. AAA tissue in culture secreted IL-6, MMP-9, and MMP-2 without any stimulation. Secretions of IL-6 and MMP-9 were enhanced by exogenous normal human immunoglobulin G (IgG), which was suppressed by Syk inhibitor, whereas secretion of MMP-2 was insensitive to IgG or Syk inhibitor.The unstimulated secretions of IL-6, MMP-9, and MMP-2 were insensitive to Syk inhibitor. These results demonstrate an important role of Syk for IgG-dependent inflammatory response in human AAA.

Free Research Field

vascular surgery

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、ヒト大動脈瘤組織の炎症および組織破壊活性がIgGによって調節され、それがSyk活性に依存することを示唆した。 本研究は腹部大動脈瘤の病態解明に有意なとともに、今後の研究で、内因性IgGも同様にSyk依存性に大動脈瘤病態に関与するか、ヒト大動脈瘤におけるSykの活性化を明らかとすることで、Sykは有望な薬物標的分子となりうると考える。腹部大動脈瘤に対するSyk阻害療法の臨床応用が期待される。