Angiogenic signaling complexes

Angiogenic signaling complexes are the functional molecular assemblies formed by the binding of pro-angiogenic or anti-angiogenic ligands to their cognate cell-surface receptors, which collectively regulate the formation of new blood vessels (angiogenesis) [1.3.1]. The most prominent of these is the complex formed between Vascular Endothelial Growth Factor (VEGF) and its receptors (VEGFR-1, -2, and -3), which triggers intracellular signaling cascades such as the MAPK/ERK and PI3K/Akt pathways to promote endothelial cell survival, migration, and proliferation [1.3.2]. Other critical complexes include those involving Fibroblast Growth Factors (FGFs), Angiopoietins (Ang-1/2) with Tie receptors, and the Notch signaling pathway [1.3.1]. In pathological conditions like cancer, an 'angiogenic switch' occurs where the overexpression of pro-angiogenic factors leads to an abundance of these complexes, facilitating tumor growth and metastasis [1.3.2]. Consequently, these complexes are major therapeutic targets; drugs like bevacizumab sequester VEGF ligands, while tyrosine kinase inhibitors like sunitinib block receptor activation [1.2.2]. However, because these pathways are also involved in normal vascular homeostasis, their inhibition can lead to systemic adverse effects such as hypertension, proteinuria, and impaired wound healing [1.2.2]. The term 'Angiogenic signaling complexes' is a collective designation for multiple distinct ligand-receptor systems rather than a single molecular target.

Other names

Angiogenesis signaling pathwaysPro-angiogenic signaling complexesAnti-angiogenic signaling complexesVEGF-VEGFR signaling axisAngiogenic receptor complexes

Drugs targeting these complexes typically function by neutralizing pro-angiogenic ligands, blocking ligand-receptor binding, or inhibiting the intracellular tyrosine kinase activity of the receptors to prevent downstream signaling cascades [1.2.2].