The role of inflammatory signal in pulmonary arterial and right ventricular remodeling of congenital heart disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15880
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Soma Katsura 東京大学, 医学部附属病院, 特任助教 (90755696)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 成人先天性心疾患 / 肺高血圧 / 右室リモデリング / 血管リモデリング / 炎症細胞 / 低酸素

Outline of Final Research Achievements

Although the prognosis of adult congenital heart disease (ACHD) has improved, the prognosis of ACHD with right ventricular dysfunction and pulmonary hypertension (PH) remains poor. Increased pulmonary blood flow in shunt disease causes significant pulmonary vascular / right ventricular remodeling, but its pathological mechanism has not been elucidated. We constructed and analyzed a mouse pathological model with increased pulmonary blood flow and hypoxia. In particular, we focused on macrophages that accumulate during the proliferative phase of vascular smooth muscle cells, and examined the functional role of this macrophage subpopulation in a shunt disease model. In this study, we showed that control of inflammation contributes to the treatment of pulmonary hypertension through analysis of the mechanism by which inflammatory cell infiltration due to hypoxic stress exacerbates pulmonary vascular remodeling.

Free Research Field

成人先天性心疾患

Academic Significance and Societal Importance of the Research Achievements

診断治療技術の進歩により成人先天性心疾患の予後は改善しているが、一部、低酸素や肺高血圧、右室機能不全を呈する成人先天性心疾患患者の予後は悪いがその機序が明らかでない。右心不全研究においては、これまで低酸素誘導性の肺高血圧モデル、あるいは、肺動脈縮窄による圧負荷モデルが使用されてきたが、先天性心疾患で特徴的な容量負荷や肺血流増加による右室機能低下をきたす病態モデルは存在しなかった。本研究では既存の右室圧負荷モデルのみでなく、肺血流量増加による肺高血圧症と低酸素血症を合併したシャント性心疾患モデルを使用し、炎症制御が肺高血圧、右室リモデリング制御の鍵となることを明らかにした点に意義がある。