Despite significant medical advances, atherosclerosis is still the leading cause of death in Western society.  In this disorder, injury or dysfunction of the endothelium is the earliest change in the artery wall.  One parameter observed in endothelial dysfunction is an increase in endothelial layer permeability, which is thought to allow for augmented diffusion of lipids into the subendothelial space.

 

Control over vascular permeability largely depends on the presence of specialized junctions between adjacent endothelial cells.  The tight junction is the most apical of these intercellular linking junctions.  Zonula occludens-1 (ZO-1) is a tight junction associated-protein located in the submembranous region of the junction.  ZO-1 acts as a scaffold, linking the transmembrane proteins of the tight junction to the actin cytoskeleton.  It is this unique positioning of ZO-1, coupling the structural and dynamic properties of the cytoskeletal network to the paracelluar barrier, that make it a key protein in the control of endothelial layer permeability.