Identification of master regulator of osteoblast differentiation in valve calcification

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03740
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Ehime University
• Principal Investigator: Izutani Hironori 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): 2019-04-01 – 2023-03-31
• Keywords: 大動脈弁狭窄症 / 石灰化 / 骨芽細胞 / 弁膜症

Outline of Final Research Achievements

There is currently no pharmacological treatment for aortic valve stenosis (AS), and the molecular mechanisms underlying calcification of the aortic valve remain unknown. In this study, we aimed to identify the differentiation mechanism from undifferentiated interstitial cells to osteoblasts and focus on tissue calcification in the pathogenesis of AS. We also aimed to identify proteins that regulate aortic valve calcification and develop inhibitors for their function. We successfully identified 12 master regulatory genes involved in osteoblast differentiation, including Notch signaling ligands. Additionally, we discovered secreted proteins that are downregulated in the vicinity of calcified tissues during the progression of AS, raising expectations for the development of novel preventive and therapeutic drugs for AS.

Free Research Field

心臓血管外科学

Academic Significance and Societal Importance of the Research Achievements

本邦における弁膜症の罹患率は年々増加傾向にあり、外科的治療法の発展のみならず新たな薬物治療法の開発は急務である。本研究は大動脈弁狭窄症の中でも特にその重症度と関連する大動脈弁石灰化の分子メカニズム解明に焦点を当てたものである。試験管内で実施した石灰化アッセイを用いて特定した１２種類の大動脈弁石灰化関連分子は、今後大動脈弁石灰化を予防または治療する薬剤の開発に応用できる可能性がある。