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Bifurcated fluid flow and shear stress at vessel bifurcations decrease endothelial permeability via nitric oxide. Transvascular flow counteracts this effect, revealing flow dynamics as key regulators of vascular function.

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Area of Science:

  • Biomedical Engineering
  • Mechanobiology
  • Cardiovascular Research

Background:

  • Endothelial barrier function is crucial for vascular health.
  • Biomechanical signals from blood flow influence endothelial cells (ECs).
  • Existing microfluidic models lack the complexity of physiological bifurcating vessels.

Purpose of the Study:

  • To develop and characterize a microfluidic model of bifurcating blood vessels.
  • To investigate the effects of hemodynamic stresses on endothelial permeability at bifurcations.
  • To elucidate the role of bifurcated fluid flow (BFF) and laminar shear stress (LSS) on EC permeability.

Main Methods:

  • Developed a microfluidic model mimicking bifurcating vessel geometry and flow.
  • Applied controlled BFF, LSS, and transvascular flow (TVF).
  • Measured changes in endothelial permeability and assessed nitric oxide (NO) dependency.

Main Results:

  • BFF at the bifurcation base significantly decreased EC permeability via NO.
  • LSS downstream of the bifurcation also reduced EC permeability through the NO pathway.
  • TVF counteracted the permeability-reducing effects of BFF and LSS.

Conclusions:

  • BFF is an important regulator of endothelial permeability at vessel bifurcations.
  • Local flow dynamics, including BFF and LSS, control vascular function.
  • NO signaling is a key mediator in flow-induced changes in endothelial barrier function.