Exploratory study of novel diagnostic and therapeutic methods targeting macrophages for aortic aneurysms

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K09593
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kagoshima University
• Principal Investigator: Miyata Masaaki 鹿児島大学, 医歯学域医学系, 教授 (00347113)
• Co-Investigator(Kenkyū-buntansha): 池田 義之 鹿児島大学, 医歯学域医学系, 准教授 (00573023) ; 赤崎 雄一 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (00631920) ; 大石 充 鹿児島大学, 医歯学域医学系, 教授 (50335345)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 大動脈瘤 / マクロファージ

Outline of Final Research Achievements

The role of macrophages in the pathogenesis of aortic aneurysms was investigated. In a mouse model of aortic aneurysm, we found that deletion of all macrophages suppressed the onset and progression of aortic aneurysm and promoted aortic aneurysm regression. Furthermore, in a mouse model of aneurysm, deletion of only activated macrophages suppressed the onset of aortic aneurysm and promoted regression of aortic aneurysm. In addition, immunohistochemistry using folate receptor β (FRβ) monoclonal antibody confirmed the presence of activated macrophages expressing FRβ in the removed aorta of patients undergoing aortic aneurysm surgery. A Kagoshima aortic aneurysm patient registry was established and blood soluble FRβ levels were measured in these patients.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

本研究において、全マクロファージや活性化マクロファージが大動脈瘤の発症、進展、抑制に関与することが明らかになった。さらに、抗FRβモノクローナル抗体に緑膿菌毒素を結合させたFRβイムノトキシンにて活性化マクロファージを抑制することで、大動脈瘤モデルマウスの大動脈瘤の発症を抑制し、大動脈瘤を退縮させたことより、FRβイムノトキシンや抗FRβ抗体薬による活性化マクロファージを標的する大動脈瘤の新規治療法の開発にも繋がる臨床的価値の高い研究結果である。