2021 Fiscal Year Final Research Report
Effects of impaired response to myocardial mitochondrial iron depletion on the development of heart failure
Project/Area Number |
19K08522
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
SATO TATSUYA 札幌医科大学, 医学部, 講師 (40592473)
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Co-Investigator(Kenkyū-buntansha) |
矢野 俊之 札幌医科大学, 医学部, 講師 (40444913)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 鉄代謝 / ミトコンドリア / 心筋症 / 慢性腎不全 |
Outline of Final Research Achievements |
Systemic iron deficiency exacerbates the prognosis of cardiovascular disease, but its mechanisms are unknown. In this study, we focused on the role of impaired response to iron deficiency in the myocardial mitochondria in the subtotal nephrectomized rat (SNx), which is a model of the failing heart with systemic iron deficiency. Contrary to decreased serum iron levels, the amount of heme iron in myocardial mitochondria was increased and oxidative stress was enhanced in SNx. Increased expression of ALAS2, a rate-limiting enzyme in the mitochondrial heme synthesis pathway and the increased production of reactive oxygen species by the Fenton reaction were suggested as mechanisms for the phenotypes. These findings indicate that impaired response to iron deficiency in the myocardial mitochondria in the failing hearts is associated with cellular death and cardiac dysfunction. Impaired mitochondrial iron response may be a novel therapeutic target for heart failure.
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Free Research Field |
ミトコンドリアを含めた代謝機能解析
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Academic Significance and Societal Importance of the Research Achievements |
本研究結果より、不全心では鉄欠乏にも関わらず心筋ミトコンドリアではむしろヘム鉄が増加する可能性が示唆された。全身性特に血清の鉄欠乏は必ずしも心筋ミトコンドリア鉄欠乏を反映しない可能性があることから、鉄補充の際には組織鉄過剰に注意が必要であること、またミトコンドリア鉄代謝異常は心不全の新規治療標的となりうることが示唆された。
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