Effects of turbulent flow on cell adhesion molecule expression in endothelial cells

Abstract

Introduction: Turbulent flow induces atherosclerosis and neointimal hyperplasia to a greater degree than arterial levels of laminar flow. Little is known regarding the effects of turbulent flow on endothelial cells (EC), including the regulation of cell adhesion molecule expression. We have previously observed that orbital flow yields two populations of cells, in the center and periphery of the culture well, corresponding to turbulent and laminar components, respectively, and suggesting the utility of this model to study differential effects of flow types. Since expression of some EC cell adhesion molecules, ICAM, are regulated by the Shear Stress Response Element (SSRE), whereas others, E-selectin, are not, we hypothesized that laminar and turbulent flow would differentially affect EC E-selectin and ICAM expression. Methods: Human umbilical vein EC were differentially seeded in either the center or periphery of culture wells. Cells were treated with or without TNF-alpha (10ng/ml) and orbital flow (210rpm) for 6 hours. E-selectin and ICAM expression were analyzed with FACS. Results: EC exposed only to orbital flow demonstrated an up-regulation of ICAM expression, despite the area of seeding. However, TNF induced E-selectin expression was down-regulated in the periphery, whereas in the center, TNF induced E-selectin expression was similar to those cells exposed to TNF but no flow (n = 3, p < 0.0001, ANOVA). Conclusions: ICAM expression is stimulated by both laminar and turbulent flow, whereas E-selectin expression is downregulated by laminar, but not turbulent flow. This suggests that laminar and turbulent flow may differentially regulate EC function both through SSRE-dependent and independent pathways.