Spatial Regulation of Inflammation by Human Aortic Endothelial Cells in a Linear Gradient of Shear Stress Export

@article{citeulike:2789329, abstract = {<b>Objective</b>: Atherosclerosis is a focal disease that develops at sites of low and oscillatory shear stress in arteries. This study aimed to understand how endothelial cells sense a gradient of fluid shear stress and transduce signals that regulate membrane expression of cell adhesion molecules and monocyte recruitment. <b>Methods</b>: Human aortic endothelial cells were stimulated with TNF-\&agr; and simultaneously exposed to a linear gradient of shear stress that increased from 0 to 16 dyne/cm². Cell adhesion molecule expression and activation of NF\&b.kappa; B were quantified by immunofluorescence microscopy with resolution at the level of a single endothelial cell. Monocyte recruitment was imaged using custom microfluidic flow chambers. <b>Results</b>: VCAM-1 and E-selectin upregulation was greatest between 2–4 dyne/cm² (6 and 4-fold, respectively) and above 8 dyne/cm² expression was suppressed below that of untreated endothelial cells. In contrast, ICAM-1 expression and NF\&b.kappa; B nuclear translocation increased with shear stress up to a maximum at 9 dyne/cm². Monocyte recruitment was most efficient in regions where E-selectin and VCAM-1 expression was greatest. <b>Conclusions</b>: We found that the endothelium can sense a change in shear stress on the order of 0.25 dyne/cm² over a length of \&sim; 10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation.}, author = {Tsou, Jean K. and Gower, Michael R. and Ting, Harold J. and Schaff, Ulrich Y. and Insana, Michael F. and Passerini, Anthony G. and Simon, Scott I.}, citeulike-article-id = {2789329}, citeulike-linkout-0 = {http://dx.doi.org/10.1080/10739680701724359}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18464160}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18464160}, doi = {10.1080/10739680701724359}, journal = {Microcirculation}, keywords = {adhesion, endothelial, gradient, inflammation, mechanoresponse, mechanosensing, microfluidic, nfkb, sensing, shear, spatial}, number = {4}, pages = {311--323}, posted-at = {2008-05-12 13:11:10}, priority = {5}, publisher = {Informa Healthcare}, title = {Spatial Regulation of Inflammation by Human Aortic Endothelial Cells in a Linear Gradient of Shear Stress}, url = {http://dx.doi.org/10.1080/10739680701724359}, volume = {15}, year = {2008} }

TY - JOUR ID - citeulike:2789329 L3 - citeulike-article-id:2789329 N2 - <b>Objective</b>: Atherosclerosis is a focal disease that develops at sites of low and oscillatory shear stress in arteries. This study aimed to understand how endothelial cells sense a gradient of fluid shear stress and transduce signals that regulate membrane expression of cell adhesion molecules and monocyte recruitment. <b>Methods</b>: Human aortic endothelial cells were stimulated with TNF-&agr; and simultaneously exposed to a linear gradient of shear stress that increased from 0 to 16 dyne/cm². Cell adhesion molecule expression and activation of NF&b.kappa; B were quantified by immunofluorescence microscopy with resolution at the level of a single endothelial cell. Monocyte recruitment was imaged using custom microfluidic flow chambers. <b>Results</b>: VCAM-1 and E-selectin upregulation was greatest between 2–4 dyne/cm² (6 and 4-fold, respectively) and above 8 dyne/cm² expression was suppressed below that of untreated endothelial cells. In contrast, ICAM-1 expression and NF&b.kappa; B nuclear translocation increased with shear stress up to a maximum at 9 dyne/cm². Monocyte recruitment was most efficient in regions where E-selectin and VCAM-1 expression was greatest. <b>Conclusions</b>: We found that the endothelium can sense a change in shear stress on the order of 0.25 dyne/cm² over a length of &sim; 10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation. IS - 4 JF - Microcirculation EP - 323 TI - Spatial Regulation of Inflammation by Human Aortic Endothelial Cells in a Linear Gradient of Shear Stress PB - Informa Healthcare VL - 15 SP - 311 KW - adhesion KW - endothelial KW - gradient KW - inflammation KW - mechanoresponse KW - mechanosensing KW - microfluidic KW - nfkb KW - sensing KW - shear KW - spatial AU - Tsou, Jean AU - Gower, Michael AU - Ting, Harold AU - Schaff, Ulrich AU - Insana, Michael AU - Passerini, Anthony AU - Simon, Scott PY - 2008/// UR - http://dx.doi.org/10.1080/10739680701724359 ER -