Cdc42 Regulates the Restoration of Endothelial Adherens Junctions and Permeability

The endothelial adherens junction (AJ) complex consisting of VE-cadherin and its associated catenins is a major determinant of fluid, solute, and plasma protein permeability of the vessel wall endothelial barrier. Impairment of endothelial barrier function contributes to cardiovascular diseases such as vascular inflammation and atherosclerosis. Adherens junctions disassemble in response to proinflammatory mediators, producing an increase in endothelial permeability; however, AJs also have the capacity to reassemble, leading to restoration of endothelial barrier function. Activation of Cdc42, a member of the Rho family of monomeric GTPases, is an essential signal regulating reannealing of AJs and reversal of the increase in endothelial permeability. The possibility of activating Cdc42 therapeutically represents a novel approach to prevent inflammatory diseases resulting from breakdown of the endothelial barrier. This review summarizes recent findings concerning the role of Cdc42 in restoring endothelial barrier integrity.