Control of endothelial barrier function by regulating vascular endothelial-cadherin.

Proper control of endothelial cell contacts is the basis for maintenance of the vascular barrier function. Loss of this function leads to leak of fluid and protein from the vasculature and extensive leaks cause shock and death. The endothelial barrier also controls the entry of leukocytes into tissue and it is believed that leukocytes target endothelial cell contacts to reach sites of inflammation. Within the last 2 years several new molecular players and molecular interactions have been identified that either help in stabilizing the endothelial contacts or mediate their opening if triggered by the appropriate stimuli. Novel signaling mechanisms have been identified that regulate endothelial cell contacts. Whether, how and to what extent the complex of the endothelial specific adhesion molecule vascular endothelial-cadherin and its associated catenins is involved in these processes will be a major focus of this article. Endothelial cell contacts are regulated by a complex interplay between various receptors and signaling mediators that control the plasticity of the cytoskeleton and the function of junctional adhesion molecules. Knowing and understanding the essential players of this network will allow development of agents that could prevent breakdown of the vascular permeability barrier in shock or that could block leukocyte extravasation and thereby antagonize inflammation.