Vascular endothelial cadherin – fibrin fragment E1 interface (VE-cadherin – fibrin E1 interface)

The Vascular endothelial cadherin – fibrin fragment E1 interface is a specialized protein-protein interaction that plays a pivotal role in the regulation of vascular integrity during inflammation (Petzelbauer et al., Nature Medicine, 2005). Vascular endothelial cadherin (VE-cadherin), also known as CD144, is a transmembrane protein essential for maintaining the adherens junctions between endothelial cells (UniProt P33151). During tissue injury or infection, the coagulation cascade is activated, and subsequent fibrinolysis generates fibrin degradation products, including the E1 fragment which contains the Bβ15-42 sequence (Orlova et al., J. Thromb. Haemost., 2011). This fragment binds to the first extracellular domain of VE-cadherin, triggering a signaling cascade that leads to the internalization of VE-cadherin and the breakdown of the endothelial barrier, resulting in capillary leak and edema (Gröger et al., J. Thromb. Haemost., 2009). Therapeutic strategies targeting this interface, such as the peptide FX06 (Tiprelestat), act as competitive inhibitors to block this interaction, thereby stabilizing the blood vessel wall and reducing inflammation-induced tissue damage (ClinicalTrials.gov NCT04389385). This target is particularly relevant in the context of acute conditions characterized by severe vascular leakage, such as myocardial reperfusion injury, acute respiratory distress syndrome (ARDS), and severe COVID-19 (Zhang et al., Frontiers in Physiology, 2020).

Other names

VE-cadherin-Bβ15-42 interactionCDH5-fibrin E1 interfaceVascular endothelial cadherin-fibrin interactionCD144-fibrin interactionBβ15-42-VE-cadherin interface

Competitive inhibition of the binding between the N-terminal of the fibrin beta chain (Bβ15-42) and the extracellular domain 1 (EC1) of VE-cadherin (Petzelbauer et al., Nature Medicine, 2005).