Endothelial hyperpermeability is associated with pathogenesis of a several diseases including diabetes, atherosclerosis, and sepsis. The mechanism underlying this process is the existence and excessive leakage of plasma rich protein fluids across the endothelial barrier. The maintenance of barrier function is critical to maintain the role of vascular endothelium as a barrier. However, a number of inflammatory mediators are found to contribute towards endothelial dysfunction. The key mechanisms that lead to defective endothelial barrier function are disintegration of endothelial cell-cell junctions as well as remodeling of action cytoskeleton, resulting in the formation of intracellular gaps that mediate transendothelial migration. Great progress has been made in understanding the underlying processes that include activation of intracellular signaling molecules involved in endothelial barrier disturbance. Thus, by seeking an agent which targets the signaling molecules that disrupt the endothelial-junction-cytoskeleton, may help to establish a therapeutic potential to enhance endothelial barrier function during inflammation.
