Elucidation of molecular mechanism and development of novel diagnostic methods for aortic valve stenosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10631
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Ehime University
• Principal Investigator: Hironori Izutani 愛媛大学, 医学系研究科, 教授 (90419200)
• 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)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 大動脈弁狭窄症 / 大動脈弁 / 石灰化 / AS / 間質細胞

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.

Free Research Field

心臓血管外科学

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。