Novel therapuetic and diagnostic approaches for monosodium urate crystal induced coronary vascular inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17511
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tohoku University
• Principal Investigator: Nishimiya Kensuke 東北大学, 大学病院, 助教 (10734238)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 尿酸 / 炎症 / 結晶 / OCT / 痛風 / 高尿酸血症 / インターロイキン / 冠動脈

Outline of Final Research Achievements

Coronary crystalline components induce macrophage chemotaxis, helping them secreting inflammatory cytokines via inflammasome activation. Cross-polarized micro optical coherence tomography (CP-uOCT) is a novel diagnostic approach to pursue birefringent crystals, such as monosodium urate crystals (MSU), in situ. MSU is known to induce local inflammation at a site of gouty tophus. Aims of this study were 1) to develop a novel pig model with highly MSU depositions to his/her coronary arteries, and 2) to attest catheter-based CP-uOCT imaging in the model in vivo. Although we were successful to develop the pig model at acute phase, it was difficult to keep the pigs due to severe vascular injury made to the coronary artery. We then developed another animal model of atherosclerosis. Rabbits were fed with high-fat diet to receive balloon injury to their iliac arteries. The models exhibited cholesterol crystal depositions. The crystal deposition was increased over time from 1 month to 3 months.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

尿酸やコレステロール結晶による血管炎症を実臨床、ヒト生体内で画像化する技術を確立することで、従来の概念とは異なるハイリスクの虚血性心疾患患者を抽出することが期待できる。また、好中球NETs/NETosiがマクロファージを主体とする結晶性炎症に支持的に作用することが動物実験レベルで証明できれば、これらに阻害的に作用する薬剤の開発につなげることができ、将来的に結晶性炎症を標的とした新しい抗動脈硬化治療戦略に帰結させることができる。