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 vasculogenesis. This paper reviews the molecular data on the multiple forms of VEGF, their signalling and accessory receptors. Five genes encoding VEGF-like proteins have been identified; the different isoforms of each VEGF molecule are generated by alternative splicing mechanisms. The different VEGF's recognize signalling tyrosine kinase receptors (Flt-1, Flk-1 and Flt-4) and accessory receptors. VEGF expression is stimulated by hypoxia-dependent and -independent mechanisms. Hypoxic responses are mediated by specific transcription factors that are expressed in a tissue dependent fashion and that are developmentally regulated. VEGF is thought to play a role in tumor angiogenesis and may contribute to cardioprotection in ischemic heart -diseases. Its role in pulmonary hypertension induced by chronic hypoxia is discussed. This review also stresses the difficulty of applying results from in vitro -studies to in vivo situations.
Frelin
C
C
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411. Sophia Antipolis, 660, route des Lucioles, 06560 Valbonne, France.
Ladoux
A
A
D'angelo
G
G
D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia; D008222:Lymphokines / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic; D012326:RNA Splicing; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors