Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and <i>N</i> -cadherin balance in mural cell–endothelial cell-regulated barrier function

Abstract

Significance Organ homeostasis requires integrity of blood vessels; alterations or disruption of the vascular barrier between blood and tissue contribute to numerous diseases. Endothelial cells and mural cells are two key cell types, which play significant roles for the maintenance of barrier function. Here, we present a 3D bicellular vascular model to mimic this barrier function and study the role of mural cells in vascular inflammation. Importantly, by using this 3D model we identified RhoA, Rac1, and N -cadherin as important regulators in mural–endothelial cell-mediated vascular barrier function. Given the recognized fundamental importance of this barrier in numerous disease settings, this in vitro microphysiological system presented herein could provide a tool for studying vascular barrier function in 3D microenvironments.