Steady unidirectional laminar flow inhibits monolayer formation by human and rat microvascular endothelial cells

Abstract

Endothelialization of artificial vascular grafts is rapid and complete in numerous animal models, including dogs and rats, but not in human patients. One possible explanation for this well-known, yet puzzling observation might be that monolayer formation of human endothelial cells (ECs), and of canine or rodent ECs, is affected differently by flow-induced shear stress. To begin testing this hypothesis, the authors wounded confluent monolayers of cultured rat and human ECs and exposed these cultures for 20 h to unidirectional steady laminar shear stress of 10 dyn/cm(2) induced by fluid flow perpendicular to the wound boundaries. In comparison to experimental control cultures simultaneously maintained under static (no-flow) conditions, flow-induced shear stress attenuated the monolayer formation (sheet migration) in both human and rat ECs. In brief, compared to control, the average human EC monolayer formation under shear was reduced by 33% whereas the average rat EC monolayer formation was reduced by 34%. Furthermore, the cell responses showed a dependence on fluid flow direction that differed per species. When exposed to shear stress, human EC monolayer formation was reduced by 16% in the upstream direction (opposing the direction of flow) and reduced by 50% in the downstream direction (with the direction of flow), whereas rat EC monolayer formation was reduced by 64% upstream and showed no change downstream. These findings suggest that although overall monolayer formation is inhibited by fluid-induced shear stress to the same extent in both species, there are cell type- and/or species-dependent migration responses to fluid-induced shear stress, and that different flow conditions possibly contribute to species-specific patterns of endothelialization.