Vascular endothelial growth factors and angiogenesis

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.