Challenges in elucidating the linkage between iron metabolism regulation/transformation and cardiac physiology/pathophysiology and its molecular mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19533
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Oike Yuichi 熊本大学, 大学院生命科学研究部(医), 教授 (90312321)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 鉄代謝制御 / 加齢

Outline of Final Research Achievements

The significance of iron metabolism and its alteration in cardiomyocytes due to aging changes was investigated in a mouse model. The level of ferrous iron in the heart tissue of aged mice showed significant decrease compared with young mice. The present study focused on the reduction of ferrous iron in aged hearts. Cardiac function analysis was performed using aged transgenic mice with elevated ferrous iron levels in cardiomyocytes. The results demonstrated a significant increase in left ventricular ejection fraction and heart wall, but no significance of left ventricular diastolic dysfunction. Furthermore, although there was an increase in oxidative stress and heart failure markers, no differences were found in antioxidant increases or survival analysis. A sustained increase in myocardial ferrous iron enhances cardiac function, but might also contribute to the pathological progression of heart failure.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

加齢マウスにおいて心臓で減少する2価鉄を増加させることにより心機能亢進を認めたが、心不全マーカーの上昇を認め、心不全の前段階の可能性が考えられた。しかし、運動耐容能や生存解析には差異を認めなかったことより、心筋細胞における2価鉄増加は加齢による心不全病態発症の新規予防法・治療開発への可能性が示唆される。今後、2価鉄増加による心収縮亢進のメカニズムも含め、さらなる検討が必要と考えられる。