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Real-time Imaging of Endothelial Cell-cell Junctions During Neutrophil Transmigration Under Physiological Flow
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Published on: August 14, 2014

Endothelial cell sensing of flow direction.

Chong Wang1, Brendon M Baker, Christopher S Chen

  • 1Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|July 2, 2013
PubMed
Summary

Endothelial cells sense blood flow direction relative to their axis, influencing inflammatory responses. Cell alignment is crucial for preventing inflammation in disturbed flow conditions.

Keywords:
atherosclerosishemodynamicsmechanotransduction, cellular

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Area of Science:

  • Cardiovascular Biology
  • Cellular Mechanotransduction
  • Endothelial Cell Biology

Background:

  • Atherosclerosis develops in arterial regions with disturbed blood flow, characterized by low shear stress and changing flow direction.
  • Endothelial cells lining arteries are exposed to these complex flow patterns, but how they sense flow direction and its impact on inflammation remains unclear.

Purpose of the Study:

  • To investigate how endothelial cells perceive and respond to changes in blood flow direction.
  • To elucidate the mechanisms by which flow direction influences endothelial cell inflammatory activation.

Main Methods:

  • Utilized a novel flow system enabling precise control over flow direction changes.
  • Examined endothelial cell responses, including endothelial nitric oxide synthase (eNOS) and nuclear factor-kappa B (NF-κB) activation, under varying flow angles.
  • Assessed responses in aligned and randomly oriented cells, as well as cells on micropatterned substrates under oscillatory flow.

Main Results:

  • Endothelial cell responses are dictated by the angle between flow direction and the cell's morphological/cytoskeletal axis.
  • Activation of atheroprotective eNOS pathways is maximal at 180° and absent at 90° flow angles.
  • Proinflammatory NF-κB activation is maximal at 90° and absent at 180° flow angles, with similar trends observed in randomly oriented cells.

Conclusions:

  • The angle of blood flow relative to the endothelial cell axis determines specific cellular responses, including protective or inflammatory pathways.
  • Impaired endothelial cell alignment in disturbed, low, or oscillatory flow conditions is a critical factor leading to inflammatory activation.