| Project/Area Number |
18K08505
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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 54040:Metabolism and endocrinology-related
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| Research Institution | University of Toyama |
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Principal Investigator |
Yagi Kunimasa 富山大学, 学術研究部医学系, 准教授 (30293343)
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| Co-Investigator(Kenkyū-buntansha) |
戸辺 一之 富山大学, 学術研究部医学系, 教授 (30251242)
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | CD206 / 心筋症 / 繊維化 / M2マクロファージ / 肥満心筋症 / 慢性心不全 / 心不全 / 糖尿病 |
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| Outline of Final Research Achievements |
We have found that mice genetically deficient in CD206, a marker of M2 macrophages, could be a cardiomyopathy model. The relationship between macrophages and heart failure has been discussed only with inflammation and damage repair, including myocarditis. Our results showed cardiac hypertrophy, increased expression of BNP, and myocardial fibrosis-related genes in MRI, echocardiography, and tissue. Although CD206 is expressed in the myocardium, tissue macrophages in the myocardium were confirmed to affect by CD206 KO. Furthermore, myocardial hypertrophy was more pronounced in the regular diet than in the high-fat diet. Thus, loss or decreased expression of CD206 leads to myocardial hypertrophy through myocardial fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義の第一としては、従来サルコメア蛋白の異常による心筋症モデルしか存在していなかった所で、M2マクロファージのマーカーであるCD206をノックアウトしたり欠損したりしたモデルが心筋繊維化を促進させBNP上昇を示す心筋症類似病態を呈するということが明らかとなったことが挙げられる。当初の推測とは逆で、高脂肪食と正常食では、むしろ正常食で心筋肥大が顕著であったことも興味深い。本モデルの検討を進めることにより、特に生活習慣病を背景とする心筋拡張障害の病態の解明や新規治療の可能性が広がることが期待される。
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