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Fluid forces control endothelial sprouting.

Jonathan W Song1, Lance L Munn

  • 1Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 31, 2011
PubMed
Summary
This summary is machine-generated.

Endothelial cells (ECs) integrate fluid forces and vascular endothelial growth factor (VEGF) gradients to control blood vessel formation. Fluid shear stress and interstitial flow direct EC sprouting and morphogenesis during angiogenesis.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Physiology

Background:

  • Angiogenesis, or new blood vessel formation, is crucial for healing and disease but its regulation is not fully understood.
  • Vascular endothelial cell growth factor (VEGF) influences vessel dilation and sprouting, yet other signals likely guide specific behaviors like sprouting or quiescence.
  • Mechanical forces from blood flow are potential regulators of vascular morphogenesis, but their interaction with VEGF in angiogenesis is unclear.

Purpose of the Study:

  • To investigate how mechanical fluid forces and vascular endothelial growth factor (VEGF) gradients cooperate to regulate endothelial cell (EC) behavior during angiogenesis.
  • To elucidate the roles of fluid shear stress and interstitial flow in controlling EC sprouting and morphogenesis.
  • To determine how ECs integrate mechanical and biochemical signals to achieve varied outcomes like sprouting or vessel dilation.

Main Methods:

  • Utilized a microfluidic tissue analog to model angiogenic sprouting in vitro.
  • Applied controlled fluid shear stress and interstitial flow conditions to endothelial cell cultures.
  • Manipulated vascular endothelial growth factor (VEGF) gradients to observe effects on endothelial cell behavior and sprout formation.

Main Results:

  • Fluid shear stress, mimicking blood flow, inhibited EC sprouting via a nitric oxide-dependent pathway.
  • Interstitial flow, simulating extravasating plasma, directed endothelial cell morphogenesis and promoted sprout formation.
  • Positive VEGF gradients stimulated EC sprouting, whereas negative gradients induced sheet-like migration, akin to vessel dilation.

Conclusions:

  • Endothelial cells (ECs) dynamically integrate mechanical cues from fluid forces with biochemical signals from vascular endothelial growth factor (VEGF) gradients.
  • Fluid forces play a critical role in modulating EC sprouting and directing morphogenesis during angiogenesis.
  • The interplay between fluid forces and VEGF gradients allows ECs to execute diverse functions, including vessel sprouting and dilation.