The role of Hippo pathway transcriptional co-activator, YAP1 in the pathogenesis of Atherosclerosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06703
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Hokkaido University of Science
• Principal Investigator: TAKAGURI AKIRA 北海道科学大学, 薬学部, 准教授 (90623710)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 動脈硬化 / 血管平滑筋細胞 / YAP1 / 炎症 / 内膜肥厚

Outline of Final Research Achievements

Yes-associated protein (YAP)1 is regulated by Hippo pathway, which controls cell survival and cell death in vascular smooth muscle cells. In this study, we investigated the role of YAP1 on the progression of atherosclerosis using a smooth muscle specific YAP1-KO mouse. Smooth muscle specific YAP1-KO mice showed decreased neointima formation induced by injury in carotid artery. Also, activation of YAP1 causes cell proliferation mediated by the phosphorylation of Akt in vascular smooth muscle cells. Accordingly, it suggests that YAP1 is a critical molecules for the pathogenesis of atherosclerosis.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、血管平滑筋細胞のYAP1が、内膜の障害により生じる内膜肥厚形成に重要な働きをすること、その機序としてAktの活性化に影響を与えることを明らかにした。本研究の成果は、YAP1が動脈硬化の形成・進展に重要な役割をもつことを示唆するものであり、これら疾患に対する新たな治療戦略を提唱に繋がる所見と考えられる。また、将来的には、YAP1の活性化と関連する疾患、がん、関節リウマチなどの疾患への応用展開に繋がることが期待される。