Exploratory research on novel biomarker and therapeutic target for pulmonary hypertension with a focus on inflammation especially in RAGE

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17658
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Shujitsu University
• Principal Investigator: Izushi Yasuhisa 就実大学, 薬学部, 講師 (80791847)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 肺高血圧症 / 慢性血栓塞栓性肺高血圧症 / 肺炎症 / HRG / sRAGE / 平均肺動脈圧

Outline of Final Research Achievements

Chronic thromboembolic pulmonary hypertension (CTEPH), an intractable disease, urgently requires the development of biomarkers and treatments based on new perspectives. In this study, pre- and post-treatment plasma from CTEPH patients whose severity of disease, as measured by mean pulmonary arterial pressure, improved markedly with treatment, was used to assess the quantitative variability. It was found that HRG was significantly lower and sRAGE was significantly higher in the plasma of patients with severe CTEPH than in healthy controls, and that both factors could be significantly improved to the same level as in healthy subjects owing to a marked improvement in the severity of the disease after treatment.

Free Research Field

薬物治療学、肺炎症、肺高血圧症、精神神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究により，CTEPH患者の治療前の平均肺動脈圧を指標とする重症度が極めて高い状態と治療後の顕著な改善によって血漿中のHRGとsRAGEが有意に変動し，治療後は健常者と同じレベルに改善する可能性が見出された．従って，この両因子の重症度に応じた量的変動はCTEPHの肺動脈特異的な閉塞病変の病態にこれらの炎症関連分子が何らかの形で関与している可能性が考えられる．この研究成果を発展させ，CTEPHの病態形成におけるHRGとRAGEの役割を解明することは学術的意義があり，さらに臨床的指標との関係性を明らかにしていくことは今後のCTEPHの新たな治療戦略の基盤となる可能性があると考えられる．