Study of Molecular Mechanisms of Heart Failure

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Niigata University
• Principal Investigator: Komei Tanaka 新潟大学, 医歯学総合研究科, 客員研究員 (70572725)
• Co-Investigator(Kenkyū-buntansha): 南野 徹 新潟大学, 医歯学系, 教授 (90328063)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 心不全 / ミトコンドリア

Outline of Final Research Achievements

The prognosis of severe heart failure is unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. We examined endomyocardial biopsies and metabolomic analysis in patients with idiopathic dilated cardiomyopathy (IDCM). Patients were classified as non-responders when the left-ventricular (LV) ejection fraction and LV end-diastolic dimension did not show more than 10% improvement over the long-term after cardiac biopsy. We here demonstrate that reduction of mitofusin-1 expression impairs cardiomyocyte metabolism and may have a crucial role in the pathology of non-responsive IDCM.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

その心不全はあらゆる心臓病の終末像であり、種々の薬物療法（β遮断薬、アンギオテンシン変換酵素阻害薬、アンギオテンシンII受容体拮抗薬、アルドステロン拮抗薬）や非薬物療法（心臓再同期療法、非侵襲的陽圧換気療法）が進歩した現在においても、癌とともに未だに予後不良な疾患群の一つである。本研究はこのような治療抵抗性の心不全患者に対する新たな治療の開発へつながるものである。