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Related Experiment Videos

Fluid shear stress threshold regulates angiogenic sprouting.

Peter A Galie1, Duc-Huy T Nguyen2, Colin K Choi3

  • 1Departments of Bioengineering,Physiology, and.

Proceedings of the National Academy of Sciences of the United States of America
|May 21, 2014
PubMed
Summary

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A specific shear stress threshold triggers new blood vessel growth (angiogenic sprouting). This flow-induced mechanism is crucial for regulating vascular density and is mediated by matrix metalloproteinase 1.

Area of Science:

  • Physiology
  • Biomedical Engineering
  • Cell Biology

Background:

  • Capillary bed density and architecture are influenced by metabolic demand and blood flow.
  • Understanding the precise mechanisms controlling angiogenesis is vital for therapeutic development.

Purpose of the Study:

  • To identify and characterize a flow-induced shear stress threshold that initiates angiogenic sprouting.
  • To investigate the role of endothelial cell-cell junctions and matrix metalloproteinase 1 in flow-mediated angiogenesis.

Main Methods:

  • Microfluidic control of fluid mechanics to precisely regulate shear stress.
  • Experimental manipulation of endothelial cell-cell junctions using VE-cadherin antagonism.
  • Finite-element modeling to predict fluid shear patterns in various geometries.
Keywords:
angiogenesisforcemechanotransductionmigrationmorphogenesis

Related Experiment Videos

  • Experimental validation of predicted sprouting patterns.

    • Main Results:

    • A shear stress threshold of 10 dyn/cm² for intraluminal and transmural flow was identified, triggering endothelial cell sprouting.
    • This threshold was independent of cell-cell junction maturation or pressure gradients.
    • Transmural and luminal flow induced matrix metalloproteinase 1 expression, which was essential for sprouting.
    • Continuous flow was necessary to sustain sprouting and prevent retraction.
    • Sprouting was directed towards paths of draining interstitial fluid flow, guided by transmural flow.
    • Increased luminal shear in vessel constrictions triggered sprouting, potentially normalizing shear stress.

    Conclusions:

    • Shear stress acts as a critical regulator of angiogenic sprouting through a defined threshold mechanism.
    • Matrix metalloproteinase 1 is a key mediator of flow-induced angiogenesis.
    • This mechanism offers insights into the spatial patterning of new blood vessels and vascular density regulation.