Establishment of in vivo imaging and research for novel heart failure therapy targeting metabolism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Osaka University
• Principal Investigator: Kioka Hidetaka 大阪大学, 医学系研究科, 助教 (70642099)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: エネルギー代謝 / イメージング / 心不全

Outline of Final Research Achievements

In this study, we aimed 1)to establish in vivo imaging system for the evaluation of metabolism, 2)to obtain the proof of concept in heart failure therapy targeting energy metabolism, and 3)to categorize patients with heart failure according to the energy status. We successfully established Cr-CEST-MRI that can visualize creatine (Cr) concentration in tissues such as muscle and testis. This imaging technique can be applied to heart in near future. We focused on a protein G0s2 that enhances mitochondrial ATP production. We generated G0s2 transgenic (TG) zebrafish and demonstrated that TG fish showed ischemic tolerance with maintaining ATP production even under hypoxia. Finally, we demonstrated that nuclear imaging of cardiac mitochondrial function using Tc-MIBI can predict the response to heart failure therapy in patients with cardiomyopathy.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

心臓はエネルギーを大量に消費する臓器であり、エネルギー不足は心機能低下、つまり心不全に繋がると考えられる。本研究では、エネルギー状態の評価方法、エネルギー状態を改善させる治療法の有用性検証、そしてエネルギー状態が予後に与える影響について研究を行った。心不全の原因はさまざまであり、個々の病態に基づいた個別化医療が求められるが、本研究で開発した画像による評価法は個別化医療へ向けた層別化に有用と期待される。またエネルギー状態を改善させることで心機能の改善を狙った新たな心不全治療薬の開発に繋がると期待される。