Mind the gap: mechanisms regulating the endothelial barrier.

摘要: The endothelial barrier consists of intercellular contacts localized in the cleft between cells, which is covered by glycocalyx a sievelike manner. Both types barrier-forming junctions, i.e. adherens junction (AJ) serving mechanical anchorage and mechanotransduction tight (TJ) sealing space to limit paracellular permeability, are tethered actin cytoskeleton. Under resting conditions, endothelium thereby builds selective layer controlling exchange fluid solutes with surrounding tissue. However, situation an inflammatory response such as anaphylaxis or sepsis disintegrate post-capillary venules leading gap formation. resulting oedema can cause shock multi-organ failure. Therefore, maintenance well coordinated opening closure interendothelial junctions tightly regulated. two principle underlying mechanisms comprise spatiotemporal activity control small GTPases Rac1 RhoA balance phosphorylation state AJ proteins. In state, junctional enhanced components, actin-binding proteins, cAMP signalling extracellular cues sphingosine-1-phosphate (S1P) angiopoietin-1 (Ang-1). addition, components prevented junction-associated phosphatases including vascular protein tyrosine phosphatase (VE-PTP). contrast, mediators inhibiting cAMP/Rac1 strong activation induce finally endocytosis cleavage VE-cadherin. This results dissolution TJs outcome breakdown.