Vascular endothelial growth factor (VEGF) is a critical modulator of angiogenesis (the growth of new blood vessels). In mammals, there are 5 members of the VEGF family, with VEGF-A being the most well-studied. VEGF-A promotes angiogenesis by inducing migration of endothelial cells, promoting mitosis of endothelial cells, and upregulating matrix metalloproteinase activity. VEGF-A is regulated by hypoxia, with increased expression when cells detect an environment low in oxygen. Physiologically, VEGF induces new blood vessel formation during embryonic development, after tissue injury, and in response to blocked vessels.

VEGF also regulates pathological vessel formation, such as in tumor growth and metastases. Angiogenesis during tumor development is complex, although it is clear that VEGF plays a key role. VEGF also regulates angiogenesis in other disease states including rheumatoid arthritis (RA), osteoarthritis, diabetes, and age-related macular degeneration. In addition, circulating concentrations of VEGF are elevated in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, a monoclonal plasma cell disorder. Although the pathologic role of VEGF in POEMS is unclear, it is a useful diagnostic marker for assessing response to therapy.