Spatial variations in endothelial barrier function in disturbed flows in vitro.

Abstract

Hindered barrier function has been implicated in the initiation and progression of atherosclerosis, a disease of focal nature associated with altered hemodynamics. In this study, endothelial permeability to macromolecules and endothelial electrical resistance were investigated in vitro in monolayers exposed to disturbed flow fields that model spatial variations in fluid shear stress found at arterial bifurcations. After 5 h of flow, areas of high shear stress gradients showed a 5.5-fold increase in transendothelial transport of dextran (molecular weight 70,000) compared with no-flow controls. Areas of undisturbed fully developed flow, within the same monolayer, showed a 2.9-fold increase. Monolayer electrical resistance decreased with exposure to flow. The resistance measured during flow and the rate of change in monolayer resistance after removal of flow were lowest in the vicinity of flow reattachment (highest shear stress gradients). These results demonstrate that endothelial barrier function and permeability to macromolecules are regulated by spatial variations in shear stress forces in vitro.