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Physiol. Genomics (October 29, 2002). doi:10.1152/physiolgenomics.00016.2002
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Articles in PresS, published online ahead of print October 29, 2002
Physiol Genomics, 10.1152/physiolgenomics.00016.2002
Submitted on February 13, 2002
Accepted on October 20, 2002

Genomic analysis of the immediate/early response to shear stress in human coronary artery endothelial cells

David G Peters1*, Xi-Chen Zhang2, Panagiotis V Benos3, Elisa Heidrich-O'Hare2, and Robert E Ferrell1

1 Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
2 Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
3 Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Computational Biology and Bioinformatics, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: david.peters{at}mail.hgen.pitt.edu.

The involvement of shear stress in the pathogenesis of vascular disease has motivated efforts to define the the endothelial cell response to applied shear stress in vitro. A central question has been the mechanisms by which endothelial cells perceive and respond to changes in fluid flow. We have utilized cDNA microarrays to characterize the immediate/early genomic response to applied laminar shear stress (LSS) in primary cultures of human coronary artery endothelial cells (HCAECs). Cells were exposed, in a parallel plate flow chamber, to 0, 15 or 45 dynes/cm2 LSS for 1 hour and gene expression profiles determined using human GEM1 cDNA microarrays. We find that a high proportion of LSS-responsive genes are transcription factors and these are related by their involvement in growth arrest. These likely play a central role in the re-programming of endothelial homeostasis following the switch from a static to a shear stressed environment. LSS-responsive genes were also found to encode factors involved in vasoreactivity, signal transduction, anti-oxidants, cell cycle-associated genes and markers of cytoskeletal function and dynamics.




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