VE-cadherin

VE-cadherin

VE-cadherin, also known as vascular endothelial cadherin or CDH5, is a transmembrane protein that plays a crucial role in the formation and maintenance of endothelial cell-cell junctions. It is a member of the cadherin superfamily and is primarily expressed in endothelial cells, which line the interior surface of blood vessels.

Structure

VE-cadherin is composed of five extracellular cadherin repeats, a transmembrane domain, and a cytoplasmic tail. The extracellular cadherin repeats mediate calcium-dependent homophilic interactions with cadherins on adjacent endothelial cells, forming strong adhesive contacts. The cytoplasmic tail interacts with various intracellular proteins, such as catenins, which link VE-cadherin to the actin cytoskeleton.

Function

VE-cadherin plays a critical role in endothelial cell-cell adhesion and the maintenance of vascular integrity. It is essential for the formation and stabilization of adherens junctions, which are specialized cell-cell junctions that provide mechanical strength to endothelial monolayers. Adherens junctions also regulate endothelial permeability and control the passage of molecules and cells across the endothelial barrier.

Furthermore, VE-cadherin is involved in the regulation of endothelial cell signaling and angiogenesis. It modulates various signaling pathways, including those mediated by vascular endothelial growth factor (VEGF) and angiopoietins, which are essential for blood vessel development and remodeling. VE-cadherin also participates in the regulation of endothelial cell migration and proliferation.

Clinical Significance

Mutations or dysregulation of VE-cadherin have been associated with various vascular disorders. For example, loss-of-function mutations in the CDH5 gene can lead to hereditary hemorrhagic telangiectasia (HHT), a genetic disorder characterized by abnormal blood vessel formation and recurrent bleeding. Dysfunctional VE-cadherin has also been implicated in the pathogenesis of vascular leakage syndromes, such as acute lung injury and sepsis.

Moreover, VE-cadherin has emerged as a potential therapeutic target for anti-angiogenic therapies in cancer treatment. Disrupting VE-cadherin-mediated cell-cell adhesion can inhibit tumor angiogenesis and disrupt the tumor vasculature, thereby impeding tumor growth and metastasis.