Mechanism for development of chronic vascular inflammation in atherosclerosis by activated neutrophil

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Yoshida Masayuki 東京医科歯科大学, 統合研究機構, 教授 (80282771)
• Co-Investigator(Kenkyū-buntansha): 大坂 瑞子 東京医科歯科大学, 統合研究機構, 助教 (00581711)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 好中球細胞外トラップ / 白血球接着 / 血管炎症 / 動脈硬化症 / 好中球 / in vivoイメージング

Outline of Final Research Achievements

Neutrophil extracellular traps (NETs) are induced by activation of neutrophils, and citrullination of histone proteins in neutrophil that occurs during NETs formation were observed in LDL receptor null mice fed high-fat diet which are atherosclerosis model mice. Furthermore, it activated β2 integrin expressed in neutrophils by elevation of blood CXCL1. The expression and secretion of CCL2 significantly increased in activated neutrophils, and it caused monocyte migration. These results suggested that NET may be involved in the initiation and progression of atherosclerosis.

Free Research Field

動脈硬化、血管炎症、脂質異常

Academic Significance and Societal Importance of the Research Achievements

これまでは動脈硬化症における血管炎症反応における単球・マクロファージの重要性が言われてきたが、本研究では好中球が重要な役割を果たしていることを明らかにした点に新規性がある。さらに、好中球ヒストンシトルリン化の制御は動脈硬化症における新しい治療ターゲットとしての可能性が示唆され、動脈硬化症に対する今後の創薬や予防に役立つものと考えられる。