Identification of immune complexes specific for aortic dissection and exploration of clinical applications

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17732
• 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: Nakao Eichi 久留米大学, 医学部, 助教 (80869545)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 大動脈解離 / IgG / フィブリノーゲン / 内皮細胞 / 細胞老化

Outline of Final Research Achievements

Our team discovered that immunoglobulin (IgG) was not found in normal aortic tissue though, in dissection tissue it was locally deposited, and IgG promoted rupture death due to aortic dissection（AD）. And it was reported that cellular senescence was involved in the dysfunction of vascular endothelial cells and inflammatory response. We hypothesized that the dysfunction of vascular endothelial barrier due to cellular senescence caused IgG deposition into the aortic wall, and that humoral immunity and inflammatory response by senescent cells contributed to AD development and progression. Various senescent cells, including endothelial cells, were found in AD tissue, and administration of ABT263 that eliminates senescent cells prevented severe dissection and rupture death. Genetic analysis showed that administration of ABT263 suppressed immune and inflammatory responses.

Free Research Field

大動脈解離

Academic Significance and Societal Importance of the Research Achievements

大動脈解離の分子病態は未だ不明な点も多く、発症予測、予防、発症後の進展予防の開発のために病態解明が急がれる。近年、動脈硬化や心不全を初めとする様々な疾患における細胞老化の関与が注目されており、老化細胞に対する治療薬やワクチンの研究も進められている。本研究において、老化細胞が解離増悪に寄与しており、さらに炎症応答及び免疫応答に関与することが示唆された。老化細胞による解離増悪メカニズムが解明されることで、将来的に臨床現場において解離増悪を抑制する治療として応用できる可能性が期待される。