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

¹ Departments of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
² Center for Computational Biology and Bioinformatics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
³ University of Pittsburgh Cancer Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

The involvement of shear stress in the pathogenesis of vascular disease has motivated efforts to define 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 dyn/cm² LSS for 1 h, and gene expression profiles were 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 reprogramming 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, antioxidants, cell cycle-associated genes, and markers of cytoskeletal function and dynamics.

gene expression; atherosclerosis; endothelial cell; microarray

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