Pro-angiogenic integrins

Pro-angiogenic integrins, primarily alpha-v beta-3 (avb3), alpha-v beta-5 (avb5), and alpha-5 beta-1 (a5b1), are a class of heterodimeric cell surface receptors that play a pivotal role in the regulation of angiogenesis [PMID: 12191480]. These receptors are highly expressed on the surface of proliferating endothelial cells during the formation of new blood vessels, but are minimally expressed on mature, stable vasculature [PMID: 15121752]. By binding to extracellular matrix components like vitronectin and fibronectin via the RGD (arginine-glycine-aspartic acid) motif, they activate intracellular signaling pathways such as FAK, Src, and PI3K/Akt, which are essential for endothelial cell migration, proliferation, and survival [PMID: 11071206]. In pathological conditions, these integrins are exploited to support tumor growth, metastasis, and neovascularization in the eye [PMID: 20603020]. Consequently, they have been targeted by various therapeutic agents, including monoclonal antibodies and small molecule RGD mimetics, aimed at disrupting these interactions to treat cancer and ocular diseases [PMID: 24030255]. Despite strong preclinical evidence, clinical trials for several inhibitors, such as cilengitide, have struggled to demonstrate significant survival benefits, potentially due to the complex compensatory mechanisms of the integrin family [PMID: 17072321].

Other names

Angiogenic integrinsVascular integrinsAlpha-v beta-3 integrinAlpha-v beta-5 integrinAlpha-5 beta-1 integrinIntegrin alpha-v beta-3Integrin alpha-v beta-5Integrin alpha-5 beta-1

Antagonism of the extracellular domain to prevent binding of ligands containing the RGD (arginine-glycine-aspartic acid) motif, thereby inhibiting downstream signaling pathways such as FAK, Src, and MAPK, and inducing apoptosis in activated endothelial cells.