Novel therapeutic strategy against heart failure associated with cancer chemotherapy via the regulation of cardiac mitochondrial metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K08609
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Tenri Health Care University
• Principal Investigator: Iwai-Kanai Eri 天理医療大学, 医療学部, 教授 (20372584)
• Co-Investigator(Kenkyū-buntansha): 的場 聖明 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10305576)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: がん抑制遺伝子p53 / 心筋ミトコンドリア / 心不全 / 酸化ストレス / 遺伝子改変動物

Outline of Final Research Achievements

We aimed to investigate the mechanisms underlying the progression of heart failure associated with cancer. For this purpose, we generated several genetically engineered mouse models and found that several metabolisms and their related molecules (TP53, D-glutamate, peroxisome proliferator-activated receptor-alpha, and D-β-hydroxybutyrate dehydrogenase 1) could be a potential therapeutic target of heart failure. The inhibition of the p53-TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) pathway reduced the oxidative stress and preserved the heart function in heart failure mice model. We also demonstrated that the p53 pathway was inhibited by bovine milk orotic acid, suggesting that this agent could be a novel promising drug for heart failure.

Free Research Field

心不全エネルギー代謝研究　腫瘍循環器学

Academic Significance and Societal Importance of the Research Achievements

医学研究の進歩によりがんは必ずしも不治の病ではなくなり、また社会の高齢化による心疾患の増加のため、がんと心疾患を合併する患者の増加が問題になっており、この数年の間に腫瘍循環器学という新しい学際分野も生まれてきた。本研究でがんと心臓の間の分子生物学的メカニズムの解明を進めたことは、この新しい学際分野にとって学術的意義がある。同時に、本研究で報告した治療介入に関する新しい知見は迅速な臨床展開につながり、社会的にも意義深いと考える。