Molecular-based analysis and therapeutic development of aortic valve stenosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16396
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Ehime University
• Principal Investigator: Namiguchi Kenji 愛媛大学, 医学部附属病院, 医員 (10815343)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 大動脈弁狭窄症 / 石灰化 / 生体弁 / 骨芽細胞 / 膠原線維 / 心膜癒着組織

Outline of Final Research Achievements

The molecular mechanism of aortic valve stenosis remains unknown. Calcified aortic valves are replaced with porcine or bovine pericardium-derived bioprosthetic valves. However, the implanted bioprosthetic valves are occasionally explanted due to structural valve degeneration. In the current study, we focused on molecular mechanism underlying calcification of native and bioprosthetic valves. Comprehensive mRNA and protein expression analyses discovered oxidative stress-related proteins and glycoproteins as the master regulators of calcification. Additionally, we also found that collagen digestion might prime calcification of bioprosthetic valves. Taken together, our results contribute to the establishment of anti-deterioration therapy for valve calcification.

Free Research Field

心臓血管外科

Academic Significance and Societal Importance of the Research Achievements

大動脈弁組織において石灰化が起こる分子機構は未だに不明である。我々が実施している臨床検体を開始点としたトランスレーショナル研究は、ASの新規治療法の開発に繋がる。特に本研究で見出した石灰化関連分子はAS治療の新しい標的となる可能性があり、今後の研究が期待される。また、一方で今回新たに見出した生体弁劣化機構に関する研究成果は、今後劣化しない耐久性のある生体弁の開発に繋げることができる。