The role of endothelial Stat3 in pathogenesis of aortic dissection

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09280
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Kurume University
• Principal Investigator: Hirakata Saki 久留米大学, 医学部, 講師 (60597425)
• Co-Investigator(Kenkyū-buntansha): 林 真貴子 久留米大学, 医学部, 助教 (70725027)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大動脈解離 / 血管内皮細胞 / 免疫複合体

Outline of Final Research Achievements

Aortic dissection (AD) is a fatal disease that occurs suddenly without preceding symptoms, of which disease mechanism is unknown. Aortic tissue from human AD or mouse AD model showed activation of STAT3, a molecule that mediates inflammation. In mouse model, pathological angiogenesis was observed in a STAT3-dependent manner, which was associated with the deposition of plasma-derived factors including fibrin, immunoglobulins and complement C3. In addition, vascular protective factor adiponectin was deposited in normal aortic tissue, which disappeared upon the AD-inducing stimuli before AD development. These findings suggested that disruption of endothelial barrier function precedes AD development that leads to the deposition of immune complex that triggers destructive inflammation to promote AD.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

大動脈解離は原因不明で前兆なく突然発症し、一旦発症すると致命的になり得る重篤な疾患である。発症が予測できないため解離発症前後の病態は不明であり、逆に発症前後の病態が不明であるため発症予測の手立てがない。大動脈解離における破壊進行に重要とされる炎症応答がどのように惹起されるかは不明である。本研究では、解離発症前に血管保護機能が低下し血漿由来因子による免疫複合体が大動脈壁に沈着し、破壊性炎症を惹起することが示唆された。解離発症前の初期炎症応答に関与するイベントが明らかになったことで、発症の前段階を捉えることが可能になり病態の解明が進むと期待される。