Human vescular endothelial growth factor (VEGF) is expressed primarily by activated macrophages, keratinocytes, renal glomerular visceral epithelium and mesangial cells, hepatocytes, smooth muscle cells, Leydig cells, embryonic fibroblasts and bronchial and choroid plexus epithelium. It is also expressed by numerous tumor cells. The expression of VEGF is upregulated by phorbol ester, TGF-β and in hypoxia. The gene for human VEGF is organized into 8 exons. As a result of alternative splicing, at least 4 transcripts encoding mature monomeric VEGF containing 121, 165, 189, and 206 amino acid residues (VEGF121, VEGF165, VEGF189, and VEGF206), each preceded by a 26 amino acid residue signal peptide, have been detected. VEGF121 and VEGF165 are diffusible proteins that are secreted into the medium. VEGF189 and VEGF206 have high affinity for heparin and are mostly bound to heparincontaining proteoglycans in the extracellular matrix. VEGF is a glycoprotein which contains a potential Nlinked glycosylation site. E. coli-expressed, recombinant human VEGF is indistinguishable from natural VEGF in its in vitro biological actions, suggesting that the carbohydrate moiety may not be required for its biological activities. VEGF is a highly conserved protein that has cross-species activity. Between human, rat or bovine VEGF, 84 - 94% sequence identity has been observed.