2019 Fiscal Year Final Research Report
Establishment of prophylactic treatment for aortic disease form analyzing the mechanism of aortic aneurysmal formation and aortic dissection
| Project/Area Number |
17K10761
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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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| Research Field |
Cardiovascular surgery
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
益田 宗孝 横浜市立大学, 医学研究科, 教授 (10190365)
内田 敬二 横浜市立大学, 附属市民総合医療センター, 診療教授 (50275062)
横山 詩子 東京医科大学, 医学部, 主任教授 (70404994)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 大動脈瘤 / プロスタグランジンE2 / アンギオテンシンII / calcium chloride |
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| Outline of Final Research Achievements |
No effective pharmacological therapy to attenuate AAA progression is currently available. We reported that the prostaglandin E receptor EP4 plays roles in AAA progression.
Here, we show the effect of CJ-42794, a selective EP4 antagonist, on AAA using two mouse models (angiotensin II- and CaCl2-induced AAAs) . CJ-42794 prevented aneurysmal formation of the two mouse models.
Additionally, in smooth muscle cells isolated from human AAA tissues, stimulation of CJ-42794 inhibited PGE2-induced IL-6 secretion in a dose-dependent manner and decreased PGE2-induced MMP-2 activity. These data suggest that inhibition of EP4 has the potential to be a pharmacological strategy for attenuation of AAA progression.
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| Free Research Field |
医学
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| Academic Significance and Societal Importance of the Research Achievements |
大動脈疾患の患者数は年々増加しており生命にかかわる重症疾患である。大動脈瘤化や大動脈解離発症のメカニズムの解明や、予防法や早期介入を含めた治療法の確立は、医学的に大きな意義がある。
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