2010
DOI: 10.1007/s10439-010-0030-6
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Endothelial Gene Expression in Regions of Defined Shear Exposure in the Porcine Iliac Arteries

Abstract: The effect of hemodynamic shear stress on endothelial gene expression was investigated in the porcine iliac arteries. A novel statistical approach was applied to computational fluid dynamics simulations of the iliac artery flow field to identify three anatomical regions likely to experience high, medium, and low levels of time average shear stress magnitude. Subsequently, endothelial cell mRNA was collected from these regions in the iliac arteries of six swine and analyzed by DNA microarray. Gene set enrichmen… Show more

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Cited by 8 publications
(6 citation statements)
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“…Intersetingly, inhibition of GSK-3β is substrate dependent, where RGD-rich matrix promotes GSK-3β phosphorylation compared to collagen substrates 42 , suggesting the existence of GSK-3β/fibronectin feedback that amplifies βcat/TCF signaling. Indeed βcat, itself a gene target of βcat/TCF, is differentially regulated in relation to shear stress magnitudes in porcine iliac arteries, suggesting a complex role for hemodynamics in regulation of this pathway 46 .…”
Section: Discussionmentioning
confidence: 97%
“…Intersetingly, inhibition of GSK-3β is substrate dependent, where RGD-rich matrix promotes GSK-3β phosphorylation compared to collagen substrates 42 , suggesting the existence of GSK-3β/fibronectin feedback that amplifies βcat/TCF signaling. Indeed βcat, itself a gene target of βcat/TCF, is differentially regulated in relation to shear stress magnitudes in porcine iliac arteries, suggesting a complex role for hemodynamics in regulation of this pathway 46 .…”
Section: Discussionmentioning
confidence: 97%
“…In particular, the assumption of a linear relation between disease severity and WSS magnitude is avoided. Moreover, the method overcomes effects of the frequently-overlooked dependency between data points without having to choose arbitrary thresholds to dichotomize the data [21,22] or average over large patches.…”
Section: Discussionmentioning
confidence: 99%
“…Apart from a few studies [9], [10], [22], flow-induced gene expression in animal models have seldom been conducted under chronic and physiological conditions. On the contrary, most studies are performed in animal models with experimentally deranged shear, hence missing compensatory mechanisms operating over longer periods of time [3], [4], or in knockout animal models subjected to an atherogenic diet.…”
Section: Discussionmentioning
confidence: 99%
“…In vivo models with experimentally deranged shear are limited to evaluation of acute molecular events associated with flow disturbances, and does not allow for the capture of compensatory mechanisms operating over longer exposure times, which is more relevant for vascular disease progression. A few studies addressing the “chronic” effect of shear stress by the use of image based computational fluid dynamics (CFD) to identify anatomically separated regions being exposed to different flow patterns have been performed [9], [10], but these studies have mainly focused on endothelial biology. Although endothelial cells (ECs) are the main sensors of fluid flow, they are in a complex crosstalk with the underlying tissue [11], [12], [13], in which upcoming pathological changes become mostly apparent, inducing phenotypic changes of vascular smooth muscle cells, enabling migration and extracellular matrix (ECM) remodeling.…”
Section: Introductionmentioning
confidence: 99%