Impact of Hexokinase dissociation from mitochondria in T cells on pressure overload induced heart failure

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16144
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Miura Shunsuke 福島県立医科大学, 医学部, 助教 (90814442)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: T細胞 / ミトコンドリア / 心不全 / Hexokinase

Outline of Final Research Achievements

We aimed to clarify whether uncoupling Hexokinase 1 (HK1) from mitochondria in T cells alleviates the progression of pressure overload-induced heart failure through the suppression of Th1 and Th17. The microtubule polymerization inhibitor, nocodazole, uncoupled HK1 from mitochondria, inhibited mitochondrial respiration in Th1 and Th17, and reduced the production of inflammatory cytokines. In the mouse model of heart failure induced by transverse aortic constriction surgery, administration of nocodazole reduced effector T cells in the heart and medial lymph nodes and decreased IFN-γ production from CD4 T cells, suggesting that nocodazole may suppress inflammation associated with heart failure.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

HK1をミトコンドリアから脱重合させることは、ミトコンドリア代謝を変化させることにより、Th1細胞やTh17細胞からのサイトカイン産生を減少させ、圧負荷心不全進展を抑制することが示唆された。HK1をミトコンドリアから脱重合させる微小管重合阻害薬は、圧負荷心不全の進展を抑える可能性が考えられ、高血圧性心疾患や大動脈弁狭窄症等の後負荷が上昇し引き起こされる心不全に対する臨床応用が期待される。