| Project/Area Number |
18K08052
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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 | Meiji University of Integrative Medicine |
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Principal Investigator |
Hiroshi Asanuma 明治国際医療大学, 臨床医学講座, 教授 (20416217)
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| Co-Investigator(Kenkyū-buntansha) |
高濱 博幸 国立研究開発法人国立循環器病研究センター, 病院, 医長 (10570301)
北風 政史 国立研究開発法人国立循環器病研究センター, 病院, 客員研究員 (20294069)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 心不全 / 薬物治療 / トランスレーショナル研究 / ドラッグリポジショニング |
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| Outline of Final Research Achievements |
Dapagliflozin, an inhibitor of SGLT2, has been reported to reduce the risk of worsening heart failure (HF) than placebo, regardless of the presence or absence of diabetes. However, there are no ideas for the cellular mechanisms for the SGLT2 inhibitors (SGLT2i)-induced improvements of HF. Therefore, we investigate whether SGLT2i attenuates the progression of HF in dogs. HF is induced by rapid ventricular pacing for 6 weeks. We administered SGLT2i orally for 14 days from 4 weeks after the start of rapid ventricular pacing, with rapid pacing was continued throughout treatment. In other dogs, we administer SGLT2i orally for 6 weeks immediately after the start of rapid ventricular pacing. SGLT2i treatment improved the pathophysiology of HF. SGLT2i treatment was shown to reduce myocardial apoptosis along with increased AMP-activated protein kinase phosphorylation and decreased Bax/Bcl-2 ratio. SGLT2i could be a novel candidate to prevent the onset and progression of HF.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病の有無とは関係なく、SGLT2阻害薬ダパグリフロジンが左室駆出率の低下した慢性心不全患者の心不全入院イベントを抑制することが報告され(DAPA-HF試験)、現在、ダパグリフロジンは、慢性心不全の標準的な治療を受けているにもかかわらず症候性で、かつ左室収縮性の低下した患者に対する処方が推奨されているが、本研究成果より、心不全症状が出現する以前のリスクステージである心不全ステージAやステージBの段階で処方されることで、心不全の発症が抑制されることが示唆された。
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