| Project/Area Number |
18K08068
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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 | Kyoto University |
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Principal Investigator |
Ashida Noboru 京都大学, 医学研究科, 講師 (00538978)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 大動脈弁狭窄症 / NF-κB / 老化 / 石灰化 / 筋線維芽細胞 |
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| Outline of Final Research Achievements |
Many people suffer from aortic stenosis in Japan, however, there is no effective treatment to stop its progression because the mechanism of aortic valve calcification is completely unknown. We focused on the similarity between vascular calcification and aortic valve calcification, and we tried to explore the mechanism of AS by inducing AS in our vascular calcification mouse model in which IKKβ is deleted in myofibroblasts and vascular smooth muscle cells, and also by analyzing the myofibroblasts cultured from the skin of vascular calcification mouse model. We could make AS by stimulating aortic valve with guide wire for PCI (Percutaneous Coronary Intervention). In terms of myofibroblasts analysis in vitro, we found that deletion of IKKβ induces senescence, which would implicate the link to the mechanism of aortic valve stenosis.
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| Academic Significance and Societal Importance of the Research Achievements |
大動脈弁狭窄症（AS）は心臓流出路の重度閉塞が引き起こされる疾患である。加齢はASの強力なリスク因子であり、高齢化の進む日本においてはその罹患患者数は増加傾向にある。高度 AS 症例に対しては治療を行うが、観血的・外科的治療であるため相応のリスクが存在する。しかしながら現在のところASの進行抑制に有効であることが示されている薬物療法は存在せず、それは大動脈弁の石灰化の詳細なメカニズムは明らかにされていないために他ならない。本研究の結果は炎症制御転写因子であるNFκBがAS形成に深く関与していることを示唆する知見であり、新たな治療戦略の開発につながる可能性があると考えられる。
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