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Control of endothelial cell mechanics and blood vessel remodeling by blood flow

Research Project

Project/Area Number 23K23887
Project/Area Number (Other) 22H02624 (2022-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2022-2023)
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Phng LiKun  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (70794098)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2024: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2023: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2022: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
KeywordsEndothelial cell / Actin cytoskeleton / Blood vessel remodeling / Haemodynamic forces / Mechanobiology / Blood vessels / Morphogenesis / endothelial cell / actin cytoskeleton / mechanobiology / hemodynamic forces / Hemodynamic forces / Blood vessel remodelling / blood vessels / morphogenesis
Outline of Research at the Start

The generation of a hierarchical network of larger arteries and veins and smaller capillaries of optimal vessel density is achieved through vessel remodeling, which is regulated by haemodynamic forces. Here, we seek to unravel how haemodynamic forces remodel EC actomyosin organization and junctions to regulate EC behaviors and control blood vessel diameter in the zebrafish.

Outline of Annual Research Achievements

We have previously discovered that endothelial cells (ECs) generate different actin organizations - circumferential, mesh and longitudinal - during vessel remodelling of intersegmental vessels in the zebrafish. The manipulation of actin organization through overexpressing Wasb or ArpC specifically in ECs resulted in a decrease in circumferential and an increase in mesh actin organization, as well as an increase in vessel diameter. Time-lapse imaging shows a correlation between circumferential actin formation and vessel constriction. Additionally, laser ablation of actin cables revealed tension in circumferential but not mesh actin. Our findings therefore suggest a role of circumferential actin in generating forces that drive vessel constriction.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

Some experiments are technically challenging and require a lot of time, but we are slowly getting results.

Strategy for Future Research Activity

1)Determine the contribution of myosin II activity in driving cell shape changes.
This will be investigated by inducing single cell expression of dominant negative RhoA and Myl9b specifically in ECs at then perform cell shape analysis at 2, 3 and 4 dpf.
2)Determine whether vascular malformations are caused be defective actin cytoskeleton remodelling. This will be investigated by investigating actin cytoskeleton organization and EC shape transitions in a zebrafish model of cerebral carvenous malformations (CCM).

Report

(2 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (11 results)

All 2023 2022

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results)

  • [Journal Article] A cell-and-plasma numerical model reveals hemodynamic stress and flow adaptation in zebrafish microvessels after morphological alteration2023

    • Author(s)
      Maung Ye Swe Soe、Phng Li-Kun
    • Journal Title

      PLOS Computational Biology

      Volume: 19 Issue: 12 Pages: 1-35

    • DOI

      10.1371/journal.pcbi.1011665

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-Throughput Imaging of Blood Flow Reveals Developmental Changes in Distribution Patterns of Hemodynamic Quantities in Developing Zebrafish2022

    • Author(s)
      Maung Ye Swe Soe、Kim Jung Kyung、Carretero Nuria Taberner、Phng Li-Kun
    • Journal Title

      Frontiers in Physiology

      Volume: 13 Pages: 1-23

    • DOI

      10.3389/fphys.2022.881929

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Regulation of endothelial cell behaviours by actin cytoskeleton and hydrostatic pressure during blood vessel morphogenesis2023

    • Author(s)
      Li-Kun Phng
    • Organizer
      A*Star, Singapore
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Mechanics of vascular tube formation and diameter regulation2023

    • Author(s)
      Li-Kun Phng
    • Organizer
      2023 GRC Angiogenesis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanics of blood vessel lumenization and remodelling2023

    • Author(s)
      Li-Kun Phng
    • Organizer
      75th Annual Meeting of Japan Society of Cell Biology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanics of blood vessel lumenization and remodelling2022

    • Author(s)
      Li-Kun Phng
    • Organizer
      Biozentrum, University of Basel, Switzerland
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Mechanics of blood vessel lumenization and remodelling2022

    • Author(s)
      Li-Kun Phng
    • Organizer
      Australian Vascular Biology Meeting 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanics of blood vessel lumenization and remodelling2022

    • Author(s)
      Li-Kun Phng
    • Organizer
      Engineering Mechanics of Cell and Tissue Morphogenesis
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Imaging blood flow and endothelial cell mechanics during zebrafish vascular morphogenesis2022

    • Author(s)
      Li-Kun Phng
    • Organizer
      Kick-off Symposium of Kento Imaging Support Center
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanics of vascular tube formation and diameter regulation2022

    • Author(s)
      Li-Kun Phng
    • Organizer
      Molecular Biology Society of Japan Annual Meeting 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanics of vascular tube formation, maintenance and diameter regulation2022

    • Author(s)
      Li-Kun Phng
    • Organizer
      12th International Kloster Seeon Meeting “Angiogenesis”
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2024-12-25  

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