Elucidation of novel function of intravascular pressure in angiogenesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19689
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Internal medicine of the bio-information integration and related fields
• Research Institution: Nippon Medical School
• Principal Investigator: Fukuhara Shigetomo 日本医科大学, 大学院医学研究科, 大学院教授 (70332880)
• Co-Investigator(Kenkyū-buntansha): 西山 功一 熊本大学, 国際先端医学研究機構, 准教授 (80398221)
• Research Collaborator: Yuge Shinya
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 血管新生 / 創傷治癒 / 内腔圧 / アクチン細胞骨格 / 伸展刺激 / 細胞極性 / ゼブラフィッシュ / 蛍光イメージング

Outline of Final Research Achievements

Fluorescence-based live-imaging of angiogenesis in wounded skin of adult zebrafish showed that elongation of the injured blood vessels was actively induced from the downstream side of blood flow, while the vessels at the upstream side only marginally elongated due to the high intravascular pressure. As the underlying mechanisms, we found that intravascular pressure induced expansion of the injured upstream vessels, which mechanically stretched the endothelial cells (ECs). Furthermore, we showed that intravascular pressure-induced stretching of ECs prevented localization of Arp2/3 actin polymerization complex at leading edge, which resulted in inhibition of actin polymerization and disruption of front-rear polarity of ECs, thereby suppressing elongation of the injured upstream vessels. Thus, this study uncovers an important role of intravascular pressure in regulation of wound angiogenesis.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

我々はこれまでゼブラフィッシュ成魚を用いた皮膚創傷治癒に伴う血管新生のライブイメージングから、「創傷時血管新生では、血流に対して下流側の損傷血管のみ伸長し、上流側の血管は内腔圧が高く伸長しない」というライブイメージングでしか知りえない現象を発見した。本研究は、この発見をもとに血管新生における内腔圧の新たな役割とそのメカニズムを明らかにした点で学術的意義がある。また、本研究成果は、内腔圧をターゲットにした新たな血管再生療法の開発など、今後の医療の発展にも寄与することが期待される。