[Non-angiogenic functions of vascular endothelial growth factor]

Vascular endothelial growth factor (VEGF or VEGF-A), also named as vascular permeable factor (VPF), is a multi-functional bio-macromolecule belonging to the family of secreted glycoprotein growth factor. VEGF can induce a variety of cellular responses through two high-affinity tyrosine kinases, VEGFR1 and VEGFR2. VEGF plays a key role in the angiogenesis and development in the embryo phase, promoting the proliferation, migration, tube formation and survival of the vascular endothelial cells. In the adult phase, VEGF mainly participates in maintaining the vascular structure and regulating physiological and pathological angiogenesis. Clinical data showed that VEGF signaling inhibitors significantly induced the degeneration of the tumor vessels and reduced tumor size. Meanwhile, various side-effects also have been observed in some patients, indicating that the non-angiogenesis functions of VEGF should be greatly emphasized, especially when developing anti-cancer drugs. Several studies showed that VEGF plays essential roles in various adult organs, such as small intestine, pancreatic islets, thyroid, kidney and liver. When VEGF level in these organs is lower than normal, the complexity of capillary network will be partially degenerated. Apart from that, VEGF also promotes the bone marrow formation, tissue repair and regeneration, the maturation of ovarian, and participates in some pathological courses such as thrombosis, inflammation and ischemia. This review focuses on the non-angiogenesis functions of VEGF and briefly discusses the molecular mechanisms.