Elucidation of molecular mechanism and development of novel diagnostic methods for aortic valve stenosis
Project/Area Number |
16K10631
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cardiovascular surgery
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Research Institution | Ehime University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
坂上 倫久 愛媛大学, 医学系研究科, 講師(特定教員) (20709266)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 大動脈弁狭窄症 / 大動脈弁 / 石灰化 / AS / 間質細胞 / VIC / 弁間質細胞 / 線維化 / 弁膜症 / HB-EGF / バイオマーカー / 心臓 |
Outline of Final Research Achievements |
The main causes of AS are heart disorders such as bicuspid aortic valve and the degeneration of valves resulting from atherosclerosis. However, the medical therapy for prevention of calcification has not been established yet, because the molecular mechanism underlying calcium deposition remain unknown. In this study, we aimed to clarify the molecular mechanism and develop the novel diagnostic methods for aortic valve stenosis. As the results, we successfully identified COX-1 as a calcification-specific factor in aortic valves. When valve interstitial cells (VICs) were stimulated by osteogenic media, COX-1 was strongly induced. However, osteoblast differentiations were completely abrogated by COX1-depletion. Our data suggested that COX-1 might be novel drug target for AS treatment.
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Academic Significance and Societal Importance of the Research Achievements |
本邦において、ASの罹患率は増加傾向にある。心臓外科領域におけるAS治療は、TAVI(経カテーテル的大動脈弁留置術)の導入などにより飛躍的に進歩したが、AS発症の分子機序が不明であるため根治療法のための薬剤開発も未だ進んでいない。本研究で得られた新規知見は、この問題解決に資するものであり、今後の研究発展の可能性が大いに期待できる。
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Report
(5 results)
Research Products
(32 results)
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[Journal Article] Valve Interstitial Cell-Specific Cyclooxygenase-1 Associated With Calcification of Aortic Valves.2019
Author(s)
Sakaue T, Hamaguchi M, Aono J, Nakashiro KI, Shikata F, Kawakami N, Oshima Y, Kurata M, Nanba D, Masumoto J, Yamaguchi O, Higashiyama S, Izutani H.
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Journal Title
Ann Thorac Surg.
Volume: 19
Pages: 31717-5
Related Report
Peer Reviewed
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[Journal Article] Perivascular Adipose Tissue Angiotensin II Type 1 Receptor Promotes Vascular Inflammation and Aneurysm Formation.2017
Author(s)
Sakaue T, Suzuki J, Hamaguchi M, Suehiro C, Tanino A, Nagao T, Uetani T, Aono J, Nakaoka H, Kurata M, Sakaue T, Okura T, Yasugi T, Izutani H, Higaki J, Ikeda S.
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Journal Title
Hypertension
Volume: 70(4)
Issue: 4
Pages: 780-789
DOI
Related Report
Peer Reviewed
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[Journal Article] Proteomics-based analysis of lung injury-induced proteins in a mouse model of common bile duct ligation.2017
Author(s)
Sakaue T, Shikata F, Utsunomiya K, Fukae S, Kurata M, Nakaoka H, Okazaki M, Kawanishi Y, Kojima A, Higashiyama S, Izutani H.
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Journal Title
Surgery
Volume: 印刷中
Issue: 6
Pages: 1525-1535
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Plasminogen and fibrinogen promote calcification in bioprosthetic valve leaflets in aortic position2017
Author(s)
Tomohisa Sakaue, Hirotomo Nakaoka, Fumiaki Shikata, Jun Aono, Mie Kurata, Teruyoshi Uetani, Takashi Murakami1, Yuji Sakashita, Ai Kojima, Shunji Uchita, Takumi Yasugi, Shigeki Higashiyama, Hironori Izutani.
Organizer
31st EACTS 2017 Annual Meeting - European Association for Cardio-Thoracic Surgery
Related Report
Int'l Joint Research
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