Mechanosignalling pathways that regulate endothelial barrier function

Blood vessels are lined by a single layer of endothelial cells that provide a barrier between circulating plasma and the underlying tissue. Permeability of endothelial cells is tightly regulated, and increased permeability is associated with a number of diseases including atherosclerosis. Endothelial cells are continuously exposed to mechanical forces exerted by flowing blood and are particularly sensitive to shear stress, which is a key determinant of endothelial function. Undisturbed flow promotes endothelial resilience and reduces permeability to macromolecules whereas disturbed flow promotes endothelial dysfunction and barrier disruption. This review will outline recent advances in our understanding of how disturbed and undisturbed flow regulate paracellular and transcellular permeability and will highlight potential cellular targets that could form the basis of therapies to limit the development of cardiovascular disease.