Gene expression profile of human endothelial cells exposed to sustained fluid shear stress.
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.
Wasserman
Scott M
SM
Millennium Pharmaceuticals, Inc., South San Francisco 94080, USA.
Mehraban
Fuad
F
Komuves
Laszlo G
LG
Yang
Ruey-Bing
RB
Tomlinson
James E
JE
Zhang
Ying
Y
Spriggs
Frank
F
Topper
James N
JN
D000595:Amino Acid Sequence; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation
D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C486727:ATOH8 protein, human