- Vascular endothelial growth factor (VEGF) is a signaling protein that plays a central role in the formation of new blood vessels, a process known as angiogenesis.
- It belongs to a family of growth factors that act specifically on endothelial cells, the cells that line the inner surface of blood vessels.
- VEGF is crucial for normal physiological processes such as embryonic development, wound healing, and the formation of collateral circulation after injury. Beyond these normal functions, VEGF also contributes to pathological processes, especially tumor growth and metastasis, by providing tumors with the blood supply needed for oxygen and nutrient delivery.
- VEGF exerts its effects by binding to high-affinity tyrosine kinase receptors located on the surface of endothelial cells, primarily VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). Activation of these receptors triggers intracellular signaling pathways that promote endothelial cell proliferation, migration, survival, and the breakdown of surrounding extracellular matrix, all of which are required for the sprouting of new capillaries. In addition, VEGF increases vascular permeability, allowing plasma proteins to leak into surrounding tissues and further facilitate new vessel growth. This increase in permeability also explains why VEGF is sometimes called “vascular permeability factor” (VPF).
- The regulation of VEGF is tightly linked to oxygen levels within tissues. Hypoxia, or low oxygen availability, is a potent stimulus for VEGF production through the activation of hypoxia-inducible factor-1 (HIF-1). In conditions such as ischemic heart disease, stroke, or peripheral vascular disease, VEGF expression is upregulated as the body attempts to restore blood supply to deprived tissues. Similarly, in cancer, rapidly proliferating tumor cells often outgrow their existing blood supply, leading to hypoxia within the tumor microenvironment. This triggers VEGF release, which in turn promotes the formation of an abnormal but functional vascular network that sustains tumor progression and provides a pathway for metastasis.
- Because of its critical role in both health and disease, VEGF has become a major target in medical research and therapy. In oncology, anti-VEGF agents such as bevacizumab (a monoclonal antibody against VEGF) are used to inhibit angiogenesis, effectively “starving” tumors of their blood supply and slowing their growth. Similarly, VEGF inhibitors are employed in ophthalmology to treat neovascular eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy, where pathological angiogenesis leads to vision loss. Conversely, strategies to enhance VEGF activity are being explored in regenerative medicine, where therapeutic angiogenesis could help restore blood flow in ischemic tissues.
