Endothelial integrin (Integrin)

Endothelial integrins are a family of heterodimeric transmembrane receptors composed of alpha and beta subunits that mediate the attachment of endothelial cells to the extracellular matrix (ECM) and other cells. They play a fundamental role in vascular biology by regulating angiogenesis, cell survival, and the integrity of the endothelial barrier through bidirectional signaling (outside-in and inside-out). In pathological conditions such as cancer, specific integrins like alpha-V/beta-3 and alpha-5/beta-1 are significantly upregulated on activated endothelial cells to facilitate tumor neovascularization and metastasis. These receptors are also critical in inflammatory and cardiovascular diseases, where they modulate leukocyte recruitment and vascular permeability. Therapeutic strategies targeting endothelial integrins include monoclonal antibodies and RGD-mimetic peptides designed to inhibit ligand binding and disrupt pro-angiogenic signaling. While several candidates have reached clinical trials for oncology and ophthalmology, achieving consistent therapeutic efficacy remains a challenge due to the complex compensatory mechanisms and the dual role of integrins in both health and disease.

Other names

Vitronectin receptor (alpha-V/beta-3)Fibronectin receptor (alpha-5/beta-1)Collagen receptor (alpha-1/beta-1, alpha-2/beta-1)Laminin receptor (alpha-3/beta-1, alpha-6/beta-1, alpha-6/beta-4)Cell adhesion moleculeVascular integrin

Antagonism of ligand binding (blocking RGD or other motifs), inhibition of downstream signaling pathways (e.g., FAK/Src, PI3K/Akt), and stabilization of endothelial junctions to prevent vascular leak.