Down-Regulation of Endothelial EphrinB2 Expression by Laminar Shear Stress

Abstract

The EphB receptors and their ephrinB ligands are involved in vascular assembly and differentiation. In this study, the authors analyzed the regulation of ephrinB2 and EphB4 in response to laminar shear stress in human endothelial cells. In order to simulate different flow conditions in vitro, human endothelial cells were exposed to laminar shear stress (1 to 50 dyn/cm2 for up to 24 h) in a cone-and-plate viscometer. EphrinB2 mRNA expression is down-regulated by arterial, but not by venous, laminar shear stress in a dose-dependent manner in primary cultures of human umbilical vein endothelial cells (HUVECs) (maximum at 30 dyn/cm2, 24 h: 46% +/- 4%of internal control without shear stress, n = 16, p < .05). The down-regulation of ephrinB2 by arterial shear stress is blocked by the protein kinase C inhibitor RO-31-8220. A similar shear stress-dependent down-regulation of ephrin-B2 can be found in human coronary artery endothelial cells (HCAECs). Chronic application of laminar shear stress does not affect EphB4 expression in venous and arterial endothelial cells. The down-regulation of ephrinB2 in response to laminar shear stress may contribute to the differentiation of endothelial cells into a nonactivated phenotype.