title: Genomic analysis of immediate/early response to shear stress in human coronary artery endothelial cells.
abstract: 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.
authors.affiliation: Departments of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. david.peters@mail.hgen.pitt.edu
authors.forename: D G
authors.initials: DG
authors.lastname: Peters
authors.forename: X-C
authors.initials: XC
authors.lastname: Zhang
authors.forename: P V
authors.initials: PV
authors.lastname: Benos
authors.forename: E
authors.initials: E
authors.lastname: Heidrich-O'Hare
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
mesh_terms: D015152:Blotting, Northern; D002478:Cells, Cultured; D019295:Computational Biology; D003331:Coronary Vessels / Q000166:cytology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D017874:Immediate-Early Proteins; D014157:Transcription Factors