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Physiol. Genomics 12: 13-23, 2002. First published November 5, 2002; doi:10.1152/physiolgenomics.00102.2002
1094-8341/02 $5.00
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Received 8 August 2002; accepted in final form 16 October 2002.
Physiological Genomics 12:13-23 (2002)
1094-8341/02 $5.00 © 2002 American Physiological Society

Gene expression profile of human endothelial cells exposed to sustained fluid shear stress

Scott M. Wasserman1,2, Fuad Mehraban3, Laszlo G. Komuves1, Ruey-Bing Yang1, James E. Tomlinson1, Ying Zhang2, Frank Spriggs3 and James N. Topper1

1 Millennium Pharmaceuticals, Inc., South San Francisco 94080
2 Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305
3 CuraGen Corporation, New Haven, Connecticut 06511

Biomechanical forces can modulate endothelial phenotype through changes in gene expression. We hypothesized that physiological laminar shear stresses (LSS) act as differentiative stimuli on endothelial cells (EC) to alter gene expression, creating an antioxidant, anti-apoptotic and anti-proliferative environment. The transcriptional profile of cultured human umbilical vein endothelial cells (HUVEC) exposed to LSS was evaluated by GeneCalling; 107 genes demonstrated at least a twofold change in expression at 24 h (LSS vs. static). These flow-responsive genes represent a limited number of functional clusters that include transcription factors, antioxidants, signaling molecules, cell cycle regulators, and genes involved in cellular differentiation. Immunohistochemistry and in situ hybridization confirmed that many of these flow-responsive genes, including the novel basic helix-loop-helix transcription factor Hath6, are expressed in EC in vivo. Thus these data identify a limited set of flow-responsive genes expressed in the endothelium that may be responsible for the establishment and maintenance of the flow-adapted endothelial phenotype in vivo.

transcriptional profile; laminar shear stress; endothelium; biomechanical force; vascular biology




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