2022 Fiscal Year Final Research Report
Novel treatment for heart failure by inflammasome regulation targeting calcium-calmodulin dependent protein kinase II
| Project/Area Number |
20K17119
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | カルモジュリンキナーゼ / 心不全 / 自然炎症 / インフラマソーム / リモデリング |
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| Outline of Final Research Achievements |
We analyzed changes of caspase-1 activity in cultured cardiomyocytes associated with overexpression or suppression of CaMKII. Extracellular vesicles in the culture medium were also analyzed. Signals originated from myocardial cells induced macrophage responses through mediators such as extracellular vesicles, IL-1β and IL-18. In chronic pressure overload model and HFpEF model, inflammatory responses and fibrosis signals were significantly reduced in macrophage-specific CaMKII knockout mice compared to wild type. Chronic left ventricular myocardial remodeling was also suppressed by CaMKII knockout.
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| Free Research Field |
循環器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
マクロファージ内CaMKIIδは慢性心負荷に伴う炎症反応、線維化および心機能低下に関与しており、心筋リモデリングにおける治療標的としての有用性が示唆された。マクロファージにおけるCaMKII-インフラマソームシグナル伝達解析を継続し、同部位を標的とすることで、従来の免疫抑制薬と異なる選択的な炎症抑制治療としての心不全治療への臨床応用を目指す。
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