Fundamental research for creating specific therapy against right heart failure

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17167
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kurume University
• Principal Investigator: Ito Shogo 久留米大学, 医学部, 助教 (60647808)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 右室不全

Outline of Final Research Achievements

This study aims to create a molecular target therapy for right ventricular failure. This is because there is no specific therapy against right ventricular failure. To find a therapeutic target to improve only right heart failure, grobal gene expression analysis was performed and it was found that the alternative complement pathway is activated in the right ventricle. Next, when pulmonary artery constriction models were created in various knockout mice that inhibited the alternative complement pathway, accordingly right ventricular function was preserved, arrhythmogenicity was also suppressed. The research results have been published in Nature Communications 2023. In addition, we thought that the functional modification to immunocompetent cells would be underlying in this phenotype, therefore we focused on IL-17 and IL-22, which are secreted from Th17 cells whose functions are mainly modified by C3a, and are currently continuing analysis using knockout mice.

Free Research Field

分子生物学、循環器内科学

Academic Significance and Societal Importance of the Research Achievements

我々は、右心室の機能低下である“右室不全”の治療薬を創り出したいと思っています。なぜなら、左心機能に悪影響を与えない右室不全の特効薬は存在しないからです。我々はマウスの実験によって、補体副経路という免疫に関わるタンパク群を阻害することで、右室不全が改善することを発見しました。補体の阻害剤は既に他臓器の疾患に使用されており、それを右室不全へと応用できることを目標に、どのような機序を介して右室不全が改善したり悪くなったりするかについて更に研究を進めたいと考えています。