Arterial shear stress frequency regulates the mechanosensitive discrimination of endothelial responsiveness

Endothelial cells (ECs) possess the ability to sense biomechanical forces as well as discriminate among distinct features of shear stress functions, such as temporal and spatial gradients. Recently, we have developed an arterial shear stress model to evaluate the responsiveness of ECs to shear forces, similar those in the human arterial circulation, and to identify mechanisms and signaling pathways sensitive by arterial flow characteristics. To test EC responsiveness to arterial frequency, human umbilical vein ECs were exposed to 3 or 6 hours of arterial flow at 0.25, 0.5, 1.0, and 1.5 Hz or an equivalent time average shear stress (7.5 dyn/cm²). Here we show that arterial frequency modulates cell migratory properties and regulates the expression of four mechanically responsive genes; eNOS, matrix gla protein, MMP-1 and CTGF. Further investigation using microarray technology demonstrated a unique subset of genes regulated by the frequency component. These genes code for proteins functioning in proximal signaling, activators of transcription, metabolism, and those associated with the cytoskeleton, for example. These data demonstrate that ECs are capable of discriminating mechanical variations in arterial frequency and provide insight into mechanotrasduction mechanisms and signaling pathways utilized to sense these differences.