Investigation of molecular mechanisms and predictive blood biomarkers in aortic valve stenosis using human clinical specimens

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08585
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Ehime University
• Principal Investigator: Aono Jun 愛媛大学, 医学部附属病院, 医員 (70512169)
• 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) ; 濱口 美香 愛媛大学, 医学部附属病院, 医員 (80815928) ; 山口 修 愛媛大学, 医学系研究科, 教授 (90467580)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大動脈弁狭窄症 / 石灰化 / 網羅解析

Outline of Final Research Achievements

Aortic valve stenosis (AS), which is caused by sclerosis and calcification of the aortic valve, is one of the most common cardiac diseases with fatal outcomes such as sudden death and acute heart failure. We divided aortic valve samples obtained during aortic valve replacement surgery into calcified and non-calcified (normal and sclerotic) lesions. Two-dimensional gel electrophoresis and mass spectrometry were performed to identify the candidate molecules for therapeutic targets and predictive markers of AS. Protein molecule with a molecular weight of approximately 50 kDa was newly discovered. This molecule was strongly detected in non-calcified tissues but not in calcified tissues. These results indicate that the discovered molecule may be a potential target for anti-calcification therapy and predictive biomarker of AS.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

大動脈弁狭窄症（Aortic stenosis: AS）は心臓から全身に血液を送るための出口にある扉が肥厚し固く石灰化し開かなくなる心臓の重症疾患である。重症化すると突然死・急性心不全など命に関わる急激な転帰をたどる。高齢化の進展に伴い患者数は増加傾向にあるが、有効な治療薬は存在せず手術を実施する他ない。この理由はASの発症・進展の主体である、弁組織の変性と石灰化に関わるメカニズムがわからないことに起因する。
ASの発症・進展に関わる分子を発見することで治療戦略の開発に繋げることができると考えられる。