Pharmacotherapy development for aortic aneurysm by regulating macrophage function
Project/Area Number |
16H05425
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cardiovascular surgery
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Research Institution | Yamaguchi University |
Principal Investigator |
YOSHIMURA Koichi 山口大学, 大学院医学系研究科, 准教授(特命) (00322248)
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Co-Investigator(Kenkyū-buntansha) |
吉田 恭子 (今中恭子) 三重大学, 医学系研究科, 准教授 (00242967)
山下 修 山口大学, 医学部附属病院, 助教 (30744388)
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Research Collaborator |
HARADA Takasuke
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
|
Keywords | 大動脈瘤 / マクロファージ / 循環器 / トランスレーショナルリサーチ |
Outline of Final Research Achievements |
Despite recent improvements in therapeutic options, pharmacotherapy for abdominal aortic aneurysm (AAA) has yet to be achieved. We have investigated the role of focal adhesion kinase (FAK), a major mediator of integrin signaling pathways, in the pathogenesis of AAA. We found that FAK was highly activated in AAA wall specimens. Activated FAK was mostly localized to macrophages in the AAA walls. FAK inhibitor PF573228 significantly reduced levels of inflammatory molecules. We created the mouse model of AAA by periaortic application of CaCl2. Treatment of mice with PF573228 significantly reduced inflammatory cell infiltration and disruption of the elastic lamellae, and prevented the progression of AAA. FAK represents a novel therapeutic target for the treatment of AAA.
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Academic Significance and Societal Importance of the Research Achievements |
本研究における大動脈瘤の新たな病態機序の発見は、大動脈瘤の薬物治療法開発に繋がる可能性が高い。すなわち、FAK阻害療法が今後実用化されれば、多くの大動脈瘤患者が無侵襲に治療可能となり、患者予後の改善が期待される。また、大動脈瘤のみならず広く慢性炎症性疾患に対して、感染症の危険性の少ない新たな作用機序の抗炎症薬の提供に繋がる。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Abdominal aortic aneurysms2018
Author(s)
Sakalihasan N, Michel JB, Katsargyris A, Kuivaniemi H, Defraigne JO, Nchimi A, Powell JT, Yoshimura K, Hultgren R
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Journal Title
Nat Rev Dis Primers
Volume: 4
Issue: 1
Pages: 1-22
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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