Figure 1.

The endothelium under (patho)physiologic conditions. (A) Tight junctions, made by occludins, claudins, and JAMs, together with adherens junctions, formed by VE-cadherin, PECAM-1 and CD99 control endothelial barrier function by maintaining interendothelial junctions. Endothelial cells are connected to the vascular ECM, pericytes and VSMCs via N-cadherin and other interactions. N-cadherin activates Trio, Rac1 and also directly induces assembly of VE-cadherin junctions. Trio, as well as VE-PTP, inhibits RhoA. Additionally, VE-PTP prevents phosphorylation and subsequently degradation of VE-cadherin. NO is formed aiming to maintain a laminar flow together with the functional and intact glycocalyx. (B) Endothelial cells can become activated by disturbed flow and inflammatory mediators. VEGF activates VEGFR2 leading to internalization and degradation of VE-cadherin and TLR-activation results in NF-κB-activation. This mediates upregulation of adhesion molecules and cytokine/interferon production. This ultimately leads to leukocyte transmigration, vascular permeability, matrix degradation and angiogenesis. AJs—adherens junctions; DAMPs—damage associated molecular patterns; ECs—endothelial cells; ECM—extracellular matrix; eNOS—endothelial nitric oxide; ICAM-1—intracellular adhesion molecule-1; JAMs—junctional adhesion molecules; MMPs—matrix metallo proteinases; NO—nitric oxide; ox-LDL—oxidized low-density lipoproteins; PAMPs—pathogen-associated molecular patterns; PECAM-1—platelet endothelial cell adhesion molecule-1; TJs—tight junctions; TLR—Toll-like receptor; VCAM-1—vascular adhesion molecule-1; VE-cadherin—vascular endothelial-cadherin; VEGF—vascular endothelial growth factor; VEGFR2—VEGF receptor 2; VE-PTP—vascular endothelial protein tyrosine phosphatase; VSMCs—vascular smooth muscle cells.