Endothelial and related angiogenic signaling pathways

Endothelial and related angiogenic signaling pathways comprise a complex network of molecular interactions that regulate the formation of new blood vessels from pre-existing ones, a process known as angiogenesis (Carmeliet & Jain, 2011, Nature). The primary driver of these pathways is the Vascular Endothelial Growth Factor (VEGF) family and its associated receptors (VEGFR-1, -2, and -3), which trigger endothelial cell proliferation, migration, and survival (Ferrara, 2004, Nature Medicine). Other critical components include the Angiopoietin-Tie2 system, which regulates vessel maturation and stability, and the Notch signaling pathway, which coordinates the differentiation of endothelial cells into tip and stalk cells during sprout formation (Apte et al., 2019, Cell). Dysregulation of these pathways is a hallmark of various pathologies, most notably cancer, where tumors hijack angiogenic signaling to ensure nutrient supply and facilitate metastasis (StatPearls, 2023). In addition to oncology, these pathways play a central role in neovascular ocular diseases such as wet age-related macular degeneration and diabetic retinopathy (PubMed, PMID: 31051106). Therapeutic strategies often focus on inhibiting these pathways using monoclonal antibodies, decoy receptors, or small-molecule kinase inhibitors to starve tumors or reduce pathological vascular permeability. Common drugs targeting these pathways include bevacizumab, which binds VEGF-A, and sunitinib, which inhibits multiple receptor tyrosine kinases. While effective, targeting these pathways can lead to systemic side effects such as hypertension and impaired wound healing due to the physiological role of angiogenesis in normal tissue maintenance.

Other names

Angiogenesis signalingVascular endothelial signalingNeovascularization pathwaysVEGF signaling pathway

Inhibition of growth factor ligands or their receptor tyrosine kinases to prevent endothelial cell activation and new blood vessel formation.