Vascular Endothelial Growth Factor (VEGF) is a signal protein that stimulates the formation of blood vessels. It is a crucial regulator of both physiological and pathological angiogenesis. VEGF is produced by cells to promote the growth of new blood vessels during embryonic development, after injury, in response to muscle exercise, and to bypass blocked vessels. However, it also plays a significant role in diseases such as cancer, where it can promote the growth of blood vessels that supply nutrients to tumors.
The discovery of VEGF dates back to the 1980s when it was identified as a factor that could increase vascular permeability and was initially named Vascular Permeability Factor (VPF). Subsequent research revealed its role in angiogenesis, leading to its renaming as VEGF. The identification of VEGF marked a significant milestone in understanding the mechanisms of blood vessel formation.
VEGF is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in various in vivo models. Hypoxia, or low oxygen levels, is a major inducer of VEGF gene transcription. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGF receptors. The role of VEGF in developmental angiogenesis is emphasized by the finding that loss of a single VEGF allele results in defective vascularization and early embryonic lethality .
VEGF has several critical activities:
VEGF exists in multiple isoforms, which are produced through alternative splicing of its mRNA. These isoforms have different properties and roles in angiogenesis and vascular permeability.
VEGF gene expression is regulated by various factors:
VEGF exerts its effects through binding to its receptors:
VEGF is critical for various physiological processes:
VEGF is implicated in several pathological conditions:
Anti-VEGF therapies have been developed to treat various conditions:
Mouse anti-human VEGF antibodies are used in research and therapeutic applications to study and inhibit VEGF activity. These antibodies can bind to human VEGF and block its interaction with its receptors, thereby inhibiting its angiogenic effects. They are valuable tools in cancer research and the development of anti-angiogenic therapies .