New insights in the control of vascular permeability: vascular endothelial-cadherin and other players

Purpose of review The control of the endothelial barrier function is essential for vascular homeostasis and is mainly mediated by cell-to-cell junctions that tightly regulate permeability to plasma solutes and circulating cells such as leukocytes and tumor cells. While in some circumstances the transient dismantling of endothelial cell junctions might be beneficial, in pathological conditions, such as cancer, severe alterations of endothelial junction composition and function are detrimental, causing massive edema and increased interstitial pressure. Here, we aim to discuss the newly and most recently identified molecular mechanisms that cooperate in the control of vascular permeability. Recent findings Although the involvement of vascular endothelial-cadherin in the regulation of vascular leakage is well known, recent findings shed light on additional molecules involved in the control of vascular endothelial-cadherin phosphorylation in physiological and pathological conditions, and identified new unknown regulators of the endothelial barrier function. Summary In the past years, several studies explored the contribution of various signaling pathways in the regulation of vascular leakage. Despite encouraging results, a more comprehensive understanding of the molecular mechanisms involved in this process will define druggable targets for new therapeutic interventions to limit endothelial barrier dysfunctions.