| Project/Area Number |
18K16386
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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 55030:Cardiovascular surgery-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 大動脈瘤 / コルヒチン / 炎症 / 好中球 / エラスチン / NLRP3 / インフラマソーム / マクロファージ / 血管平滑筋細胞 / 遺伝子発現 / 薬物療法 |
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| Outline of Final Research Achievements |
The pathogenesis of aortic aneurysm (AA) is characterized by the chronic inflammation of the aortic wall with the accumulation of macrophages and the degradation of the extracellular matrix (ECM) including elastin. Colchicine (COL), which is an alkaloid derived from the plant Lily family Colchicum autumnale, is known for anti-inflammatory effects. We investigated whether COL could prevent the progression of aortic aneurysms.
Compared to saline-treated control mice, AA model mice treated with COL by oral administration exhibited suppression of dilation of aortic diameter, inhibition of elastin degradation, and down-regulation of protein levels including IL-1β, TNF-α, MCP-1, NLRP3, and neutrophil elastase.
These results suggested that COL prevents the progression of AA, suggesting that COL could be a novel therapeutic agent for treatment of AA.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦における大動脈瘤罹患患者数は、高齢者・メタボリック症候群の増加に伴い増えている。標準治療である人工血管置換術の破裂予防効果は絶大だが、手術侵襲が大きく、手術死亡率・合併症発症率は低くない。一方で手術が施行できない患者に対して大動脈瘤径拡大や破裂を回避する有効な内科的治療法はいまだ確立されておらず、有用な薬物療法の探索が望まれる。
コルヒチンは炎症性細胞の浸潤抑制やNLRP3インフラマソーム形成阻害効果を持つことが知られるが、大動脈瘤においても同様の効果を介した大動脈瘤拡大進行を遅らせる成果を得た。本研究で得られた成果は、学術的意義だけでなく臨床応用への可能性も示唆され、社会的意義を有する。
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