Inter-endothelial gap formation

Inter-endothelial gap formation is a fundamental biological process characterized by the physical separation of adjacent endothelial cells, resulting in increased paracellular vascular permeability [Schlegel & Waschke, 2014]. This phenomenon occurs when the forces generated by the endothelial actomyosin cytoskeleton (cell contraction) overcome the adhesive forces of intercellular junctions, primarily the adherens junctions composed of vascular endothelial (VE)-cadherin [Sukriti et al., 2014]. In physiological conditions, controlled gap formation is necessary for the migration of immune cells into tissues; however, its dysregulation is a hallmark of pathological states like sepsis and acute respiratory distress syndrome (ARDS), where massive fluid leakage leads to organ failure [Komarova et al., 2015]. While it is not a single molecular target, it represents the cumulative effect of various signaling cascades, such as the RhoA/ROCK, Myosin Light Chain Kinase (MLCK), and VEGF-mediated pathways. Therapeutic intervention often focuses on stabilizing these junctions or inhibiting the contractile machinery to restore the endothelial barrier [Claesson-Welsh et al., 2021].

Other names

Endothelial gap formationParacellular gap formationEndothelial barrier disruptionVascular leakageEndothelial cell retraction

Stabilization of endothelial adherens junctions and inhibition of actomyosin-mediated cellular contraction through the modulation of signaling pathways like VEGF, Rho/ROCK, and MLCK.