VEGF was discovered in 1989. Research conducted over the past 10 years has
demonstrated that VEGF is a major regulator of angiogenesis and vasculogene
sis. This paper reviews the molecular data on the multiple forms of VEGF, t
heir signalling and accessory receptors. Five genes encoding VEGF-like prot
eins have been identified; the different isoforms of each VEGF molecule are
generated by alternative splicing mechanisms. The different VEGF's recogni
ze signalling tyrosine kinase receptors (Fit-1, Flk-1 and Flt-4) and access
ory receptors. VEGF expression is stimulated by hypoxia-dependent and -inde
pendent mechanisms. Hypoxic responses are mediated by specific transcriptio
n factors that are expressed in a tissue dependent fashion and that are dev
elopmentally regulated. VEGF is thought to play a role in tumor angiogenesi
s and may contribute to cardioprotection in ischemic heart diseases, its ro
le in pulmonary hypertension induced by chronic hypoxia is discussed. This
review also stresses the difficulty of applying results from in vitro studi
es to in vivo situations.