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Vasculo-protective effects of curcumin: impact on monocyte to endothelial cell adhesion and transendothelial migration in static and in shear-stress condition
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We showed previously that curcumin decreased immune cell infiltration into intima layer of aorta in mice model of atherosclerosis (Coban et al, 2012). One important determinant of this inter-cellular interaction is the hemodynamic forces associated with blood flow, namely shear-stress. Even though a chronic exposure of endothelial cells to a laminar flow has been showed to affect endothelial cell functions, usually in-vitro studies examining cellular effects of polyphenols are performed under static conditions. The aim of this study was to assess the impact of curcumin on monocyte adhesion to endothelial cells and their transendothelial migration in both static and shear stress (SS) conditions.Primary human endothelial cells were grown under static condition or under a 1Hz-pulsatile aortic shear-stress of 7dyne/cm² to mimic as closely as possible physiological conditions. Confluent cells were exposed to low concentrations of curcumin (0.5-1μM) for 3 hours prior to their stimulation by TNF-alpha for 4 hours, then monocyte adhesion and transendothelial migration assays were carried out. NF-κB signalling pathway was investigated in static conditions performing western-blot.Pre-exposure of endothelial cells to 0.5μM curcumin under a physiological flow reduced by 40% the adhesion of THP1 monocytes while only a 25% decrease is observed in static condition. Similar effect was observed on TEM with 1μM curcumin (SS: -35% vs Static: -25%). In addition we observed an inhibition of the ratio of phosphor-p65 NF-κB to total p65 with 1μM curcumin, this without any modulation of the ratio phospho/total of the inhibitor IκBα.In conclusion, even if further experiments are needed, these results account for a modulation of the cellular effects of curcumin by the shear-stress at vascular level and suggest that curcumin could counteract part of the deleterious effects of vascular inflammation under physiologically-relevant conditions undoubtedly through the reduction of TNFα-induced activation of NF-κB.
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