2021 Fiscal Year Final Research Report
Development of new treatments for carotid stenosis targeted Nox family proteins responsed by share stress
Project/Area Number |
20K17934
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Kyushu University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2022-03-31
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Keywords | 頚動脈狭窄症 / 流れずり応力 / Noxファミリータンパク質 |
Outline of Final Research Achievements |
In cultured brain endothelial call under share stress condition, Nox4 was significantly upregulated by laminar flow compared with turbulent flow. The mRNA expression of MCP-1, a key molecule participating in chronic vascular inflammation, was significantly upregulated in Nox4-knockdown endothelial calls. Nox4 was unregulated in high glucose and no-flow condition, but this change was slow in high glucose and turbulent flow condition. On the other hand, MCP-1 was not changed in high glucose and no-flow condition, but upregulated in high glucose and turbulent flow condition. Collectively, Nox4 may reduce the inflammation of carotid artery through the downregulation of MCP-1 and this effect is diminished in hyperglycemia.
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Free Research Field |
脳血管障害
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Academic Significance and Societal Importance of the Research Achievements |
脳動脈瘤における先行研究において、我々は流れずり応力によるNox4の変化が、血管壁における炎症を抑制し保護的に作用する可能性を示したが、本研究においても同様の結果が得られ、頚動脈狭窄におけるプラーク破綻に対し、Nox4が抑制的に働く可能性が示唆された。またこの血管炎症抑制効果は高血糖など動脈硬化の危険因子がある際に、減弱する可能性も示唆された。動物モデルにおいてこれを支持するデータは得られなかったが、Nox4を賦活することによる脳梗塞予防効果を目指した新規治療法が期待される。
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