VEcadheriini

VE-cadherin (vascular endothelial cadherin), also known as *CDH5* (cadherin-5), is a classical cadherin protein primarily expressed in endothelial cells lining blood and lymphatic vessels. It plays a critical role in maintaining vascular integrity and permeability by mediating cell-cell adhesion through calcium-dependent interactions between adjacent endothelial cells. VE-cadherin is a single-pass transmembrane protein with five extracellular cadherin repeats, a transmembrane domain, and a cytoplasmic tail that binds to cytoskeletal and signaling proteins.

The extracellular domain of VE-cadherin facilitates homophilic binding, ensuring tight junctions between endothelial cells. This interaction is essential for forming the endothelial barrier, which regulates the passage of substances between blood and tissues. Disruption of VE-cadherin function, often through mutations or post-translational modifications, has been linked to vascular leakage, inflammation, and pathological conditions such as angiogenesis in tumors, diabetic retinopathy, and sepsis.

VE-cadherin’s cytoplasmic tail interacts with scaffolding proteins like β-catenin, γ-catenin (plakoglobin), and p120-catenin, which help anchor it to the actin cytoskeleton. This connection is crucial for signal transduction pathways that influence vascular permeability, cell migration, and angiogenesis. Additionally, VE-cadherin is involved in signaling cascades triggered by growth factors, such as vascular endothelial growth factor (VEGF), which can modulate its localization and function.

Studies have highlighted VE-cadherin’s role in both physiological and pathological angiogenesis. In cancer, its downregulation or altered expression can promote tumor vascularization, while its upregulation may stabilize blood vessels. Research continues to explore VE-cadherin as a potential therapeutic target for vascular-related diseases, including anti-angiogenic cancer treatments and interventions for vascular leakage disorders.