Mechanisms of reduced lifespan of erythrocytes in chronic heart failure
| Project/Area Number |
18K08055
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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 | Hyogo Medical University (2022)
Hyogo University of Health Sciences (2018-2021) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内藤 由朗 兵庫医科大学, 医学部, 講師 (10446049)
増山 理 兵庫医科大学, 医学部, 教授 (70273670)
伊藤 都裕 兵庫医療大学, 薬学部, 助教 (20767363)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 心不全 / 心腎貧血症候群 / ダール食塩感受性ラット / 貧血 / 腎不全 / フマル酸ジメチル / 酸化ストレス / 慢性心不全 / 鉄欠乏 |
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| Outline of Final Research Achievements |
Anemia in patients with chronic heart failure (CHF) is a sign of poor prognosis. However, mechanisms of anemia in CHF are thought to be multifatorial and not well understood. We examined the mechanisms of anemia in Dahl salt-sensitive (DS) rat, a model of chronic heart failure. We found that reduced lifespan of erythrocytes is the major cause of anemia. Eryptosis is a programmed death of nucleus-free, iron-filled red blood cells. We found that eryptosis induced by oxidative stress was a cause of reduced lifespan of erythrocytes in DS rats. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the cellular defense against toxic and oxidative insults. We found that dimethyl fumarate, an activator of Nrf2, prevented anemia, cardiac and renal fibrosis and inflammation, and prolonged survival in DS rats.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性心不全患者において、慢性腎不全と貧血が合併した病態は心腎貧血症候群として知られ、予後不良の因子であるが、その機序は十分解明されたとはいえず、治療法は確立されていない。我々は慢性心不全の動物モデルであるDahl食塩感受性(DS）ラットに合併する貧血と心臓・腎臓障害にフマル酸ジメチル（DMF）が有効であることを示した。DMFは多発性硬化症の治療薬としてすでに認可されており、drug repositioning により、心腎貧血症候群の治療薬の候補となりうることが示された。確立された治療法のない心腎貧血症候群に対し有効な治療法が見つかれば、その学術的・社会的意義は大きい。
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Report
(6 results)
Research Products
(9 results)
