In vivo vascular remodeling: Molecular mechanisms of blood flow sensing and response by vascular endothelial cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16140
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Suntory Foundation for Life Sciences (2022); Kyoto University (2019-2021)
• Principal Investigator: Yuta Takase 公益財団法人サントリー生命科学財団, 生物有機科学研究所・統合生体分子機能研究部, 特別研究員 (70756478)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 生体内血管リモデリング / トリ胚 / 細胞挙動 / 血流刺激 / 感知・応答

Outline of Final Research Achievements

Whereas the early formation of blood vessels is genetically determined during embryogenesis, at later stages non-genetic factors including hemodynamics (blood flow) play predominant roles in vasculature network formation, particularly the vasculature remodeling. To understand how the remodeling is regulated in living embryos at the cellular and molecular levels, I used the yolk sac vasculature in chicken embryos as an experimental model. At first, I established a local gene transfer method to developing vasculature. By taking advantages of this method, I found that the TGFβ receptor ALK1 triggers remodeling to the arteries, in association with the mechano-stress sensor TRPM7/8 and cytoskeletal regulator RhoA. These results suggest that the blood flow may be acting as the “physical stimulus”. Additionally, local knockdown experiments suggest that ALK1 may be also involved in determining the nature of blood vessels (arteries and veins) after remodeling.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

血管ネットワークは、秩序だった動静脈パターンで全身に広く分布し、各臓器・器官への酸素や栄養素の供給などを通してさまざまな生理活動を支えている。これらの血管パターンの多くは、無秩序なメッシュ状の血管網がリモデリングすることで完成する。本研究成果は、発生過程における動脈リモデリングを制御する分子機構の一端を明らかにした点で生命科学分野における学術的意義を持つ。加えて、血管リモデリングの破綻は循環器系疾患やガン転移にも繋がりうることから、本研究成果は社会的にも大きな意義を持つ。