| Project/Area Number |
18K08046
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
永井 良三 自治医科大学, 医学部, 学長 (60207975)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 心不全 / 血管老化 / 転写 / DNA損傷応答 |
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| Outline of Final Research Achievements |
Heart failure with reduced ejection fraction (HFrEF) is marked by a reduced left ventricular ejection fraction (EF) and symptoms like dyspnea, fatigue, and edema. While several pharmacological interventions exist, new treatments targeting different pathophysiological mechanisms are needed. Evidence suggests that inhibiting pyruvate dehydrogenase kinase 4 (PDK4) may be cardioprotective. We focused on vitamin K3, using its structure to create new PDK4 inhibitors with higher activity than dichloroacetic acid, and tested their effects on a mouse heart failure model. Among these, PDK4 inhibitor 8 significantly improved EF without reversing cardiac fibrosis or wall thickness. This potent PDK4 inhibitor may enhance EF by regulating bioenergetics through the activation of the tricarboxylic acid cycle.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、新規PDK4阻害剤の開発を通じて、駆出率低下型心不全（HFrEF）の治療に対する新たなアプローチを提供する学術的意義を有するものである。特に、ビタミンK3を基にしたPDK4阻害剤が既存の治療法よりも優れた効果を示し、心保護効果を持つことが証明された。社会的意義としては、HFrEF患者に新たな治療オプションを提供することで、症状の改善や生活の質の向上に寄与する可能性がある。従来の治療法では効果が限定的であった患者に対して、この新薬は新たな希望となり得る。また、心不全の治療費削減や医療資源の最適化にも貢献する可能性がある。
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