Endothelial and vascular smooth muscle cell pro-angiogenic signaling pathways

Endothelial and vascular smooth muscle cell pro-angiogenic signaling pathways represent the integrated molecular networks that drive the formation of new blood vessels from existing ones. This process, known as angiogenesis, requires the coordinated activation of endothelial cells (ECs) and the subsequent recruitment of vascular smooth muscle cells (VSMCs) for vessel stabilization. Key signaling axes include the Vascular Endothelial Growth Factor (VEGF) pathway, which stimulates EC proliferation and migration, and the Platelet-Derived Growth Factor (PDGF) and Angiopoietin-Tie2 pathways, which regulate VSMC recruitment and vascular maturation (Ferrara & Adamis, 2016; Saharinen et al., 2017). In many cancers, these pathways are pathologically upregulated by tumors to ensure a steady supply of oxygen and nutrients, facilitating tumor growth and metastatic spread. Consequently, these pathways are major therapeutic targets in oncology, with drugs like bevacizumab and sunitinib designed to inhibit specific ligands or receptors within the network (Chen & Cleck, 2009). Beyond cancer, dysregulated angiogenic signaling is a primary driver of neovascular eye diseases, such as wet age-related macular degeneration. However, because these pathways are also essential for physiological processes like wound healing and blood pressure regulation, their systemic inhibition often leads to adverse effects such as hypertension and hemorrhage.

Other names

Angiogenic signaling pathwaysVascular pro-angiogenic signalingEC-VSMC crosstalk in angiogenesisTumor angiogenesis pathways

Inhibition of pro-angiogenic signaling by targeting ligands (e.g., VEGF-A) or their respective receptor tyrosine kinases (e.g., VEGFR2, PDGFR, Tie2) to suppress endothelial cell activation and vessel stabilization (Ferrara & Adamis, 2016).