| Project/Area Number |
19K07069
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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 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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)
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| Keywords | 好中球細胞外トラップ / 血管内皮細胞 / 酸化LDL / HDL / 動脈硬化症 / リポタンパク質 / 好中球 / 血管炎症 |
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| Outline of Research at the Start |
循環器系疾患の危険因子である酸化LDLの生理的役割について、白血球系細胞への作用については不明な点が多い。好中球細胞外トラップ（NETs）は、周辺の細胞や組織に障害を与えて様々な疾患の形成に寄与することが知られ、動脈硬化にも関わることが示唆されている。本研究は好中球のNETs形成に対する酸化LDLの働きと血管細胞に及ぼす影響について解析し、動脈硬化病巣形成の新たなメカニズムの解明を目指す。
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| Outline of Final Research Achievements |
We found that endocytosis and endothelial-mesenchymal transition are involved in the morphological changes of vascular endothelial cells induced by NETs and LDL or copper-oxidized LDL. In vivo oxidized LDL promoted NET formation of HL-60-derived neutrophils more mildly than copper-oxidized LDL. Enhanced NET formation induced by copper-oxidized LDL and its components, oxidized phospholipids and lysoPC, was inhibited by the coexistence of HDL. Oxidation of HDL not only abolished these inhibitory effects but also promoted NETs formation similarly to copper-oxidized LDL.
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| Academic Significance and Societal Importance of the Research Achievements |
循環器系疾患の危険因子である酸化LDLの生理的役割について、これまでに知られているマクロファージの泡沫化を介した血管壁での脂質蓄積促進作用に加えて、好中球のNETs形成の促進とともに血管内皮の炎症惹起と形質変化を促す新たな機序が見出される可能性が示唆された。
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