The role of vascular endothelial growth factor in angiogenesis

Vascular endothelial growth factor (VEGF) is an important angiogenic factor. VEGF family includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor (PIGF) which by different interactions with three tyrosine kinase receptors, including VEGFR-1/Flt-1, VEGFR-2/Flk-1 and VEGFR-3/Flt-4, and two non protein tyrosine kinase receptors, including neuropilin-1 and -2, are responsible for endothelial cells proliferation, migration and expression of chemokines, cytokines and matrix metalloproteinases. VEGF, expressed in response to cytokines, growth factors, hormones, extracellular proteases, and hypoxia, has been detected in different tissues, such as brain, liver, spleen, kidney and skin, where it is produced by several cytotypes, including endothelial cells, fibroblasts, keratinocytes, macrophages, mast cells and tumor cells. VEGF is involved in several physiological and pathological conditions, including embryo development, vasculogenesis and early hematopoiesis, ovulation, wound repair, psoriasis, endometriosis, arteriosclerosis, diabetic retinophathy, neovascular age-related macular degeneration of the eye, chronic inflammatory diseases, and tumors. Since angiogenesis is a key event in tumor growth, invasion and metastasis, VEGF has been proposed as a therapeutic target in several tumor types, such as breast cancer, renal cell cancer, colorectal cancer and non small cells lung cancer. Furthermore, VEGF may be an interesting therapeutic agent in ischemic heart and peripheral diseases.