| Project/Area Number |
18K15867
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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 53020:Cardiology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Focal adhesion kinase / 大動脈解離 / マクロファージ / 平滑筋 / FAK |
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| Outline of Final Research Achievements |
In aortic dissection, inflammation caused by stress on the aortic wall and extracellular matrix destruction are important. We created a mouse model of aortic dissection by continuous infusion of β-aminopropionitrile and angiotensin II. In this study, we focused on focal adhesion kinase (FAK), which is an intracellular signal transduction molecule, and investigated its relationship with the pathological condition of dissociation. Administration of FAK inhibitor significantly reduced the severity of aortic dissection, especially in the aortic arch including the ascending aorta. Moreover, mortality was significantly improved by administration of FAK inhibitor. It was suggested that FAK causes tissue destruction in the aortic wall.
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| Academic Significance and Societal Importance of the Research Achievements |
大動脈解離は大動脈中膜が突然断裂する致死的疾患である。社会的責任が大きくなる50代 以上の男性に多く発症し、突然死を来すことがあるが、外科的治療の他に積極的な内科治療は存在しない。本研究の結果からFAKは大動脈壁に病理学的ストレスを伝達して組織破壊を引き起こし、大動脈解離の病因において中心的な役割を果たすことが示唆された。また、FAK阻害薬が解離の増悪抑制と死亡率減少に有効であることが明らかとなり、解離進行阻止療法の開発につながる新しい知見となった。
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