Development of novel heart failure treatment targeting NADPH oxidase component p22phox

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16080
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Nara Medical University
• Principal Investigator: Nakada Yasuki 奈良県立医科大学, 医学部, 助教 (70812379)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 心不全 / NADPHオキシダーゼ

Outline of Final Research Achievements

We researched p22phox, which forms a heterodimer with NADPH oxidase (NOX), the main source of reactive oxygen species. We found that the expression of p22phox was significantly increased in heart samples from human heart failure patients compared to healthy subjects. In addition, cardiomyocyte-specific p22phox knockout mice showed reduced expression of myocardial sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a), which plays a central role in cardiac contraction and relaxation, suggesting that p22phox is involved not only in stabilizing NOX but also in maintaining the expression of SERCA2a.

Free Research Field

循環器

Academic Significance and Societal Importance of the Research Achievements

高齢化社会を迎えた日本において，心血管疾患による死亡は癌に次いで2番目に多く，そのなかでも心不全による死亡の割合が最も多くなっている．心不全患者に対する治療薬が様々開発されているものの，未だに予後不良な疾患のままであり，従来とは異なる視点から分子メカニズムを検討する必要がある．今回の研究では心不全におけるNADPHオキシダーゼファミリーの新たな機序の解明するものであり，新規の治療薬を開発に寄与する可能性がある．