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Reviews |
a Department of Biology, Technion, Israel Institute of Technology, Technion City, Haifa 32000, Israel
Vascular endothelial growth factor (VEGF) is a highly specific mitogen for vascular endothelial cells. Five VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene. These isoforms differ in their molecular mass and in biological properties such as their ability to bind to cell-surface heparan-sulfate proteoglycans. The expression of VEGF is potentiated in response to hypoxia, by activated oncogenes, and by a variety of cytokines. VEGF induces endothelial cell proliferation, promotes cell migration, and inhibits apoptosis. In vivo VEGF induces angiogenesis as well as permeabilization of blood vessels, and plays a central role in the regulation of vasculogenesis. Deregulated VEGF expression contributes to the development of solid tumors by promoting tumor angiogenesis and to the etiology of several additional diseases that are characterized by abnormal angiogenesis. Consequently, inhibition of VEGF signaling abrogates the development of a wide variety of tumors. The various VEGF forms bind to two tyrosine-kinase receptors, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1), which are expressed almost exclusively in endothelial cells. Endothelial cells express in addition the neuropilin-1 and neuropilin-2 coreceptors, which bind selectively to the 165 amino acid form of VEGF (VEGF165). This review focuses on recent developments that have widened considerably our understanding of the mechanisms that control VEGF production and VEGF signal transduction and on recent studies that have shed light on the mechanisms by which VEGF regulates angiogenesis.—Neufeld, G., Cohen, T., Gengrinovitch, S., Poltorak, Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 9–22 (1999)
Key Words: hypoxia • angiogenesis • oncogene • heparan-sulfate proteoglycan • cytokine
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C. Cappuzzello, R. Melchionna, A. Mangoni, G. Tripodi, P. Ferrari, L. Torielli, D. Arcelli, M. Helmer-Citterich, G. Bianchi, M. C. Capogrossi, et al. Role of rat {alpha} adducin in angiogenesis: Null effect of the F316Y polymorphism Cardiovasc Res, August 1, 2007; 75(3): 608 - 617. [Abstract] [Full Text] [PDF]
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 Y. Wang, J. Chang, K.-D. Chen, S. Li, J. Y.-S. Li, C. Wu, and S. Chien Selective adapter recruitment and differential signaling networks by VEGF vs. shear stress PNAS, May 22, 2007; 104(21): 8875 - 8879. [Abstract] [Full Text] [PDF]
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 S. G. Ball, C. A. Shuttleworth, and C. M. Kielty Vascular endothelial growth factor can signal through platelet-derived growth factor receptors J. Cell Biol., May 7, 2007; 177(3): 489 - 500. [Abstract] [Full Text] [PDF]
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P. D. Jani, N. Singh, C. Jenkins, S. Raghava, Y. Mo, S. Amin, U. B. Kompella, and B. K. Ambati Nanoparticles Sustain Expression of Flt Intraceptors in the Cornea and Inhibit Injury-Induced Corneal Angiogenesis Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2030 - 2036. [Abstract] [Full Text] [PDF]
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V L Bosquiazzo, J G Ramos, J Varayoud, M Munoz-de-Toro, and E H Luque Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis Reproduction, May 1, 2007; 133(5): 1045 - 1055. [Abstract] [Full Text] [PDF]
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 A. B. Dixon, M. Knights, J. L. Winkler, D. J. Marsh, J. L. Pate, M. E. Wilson, R. A. Dailey, G. Seidel, and E. K. Inskeep Patterns of late embryonic and fetal mortality and association with several factors in sheep J Anim Sci, May 1, 2007; 85(5): 1274 - 1284. [Abstract] [Full Text] [PDF]
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D. Kong, Y. Li, Z. Wang, S. Banerjee, and F. H. Sarkar Inhibition of Angiogenesis and Invasion by 3,3'-Diindolylmethane Is Mediated by the Nuclear Factor-{kappa}B Downstream Target Genes MMP-9 and uPA that Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate Cancer Cancer Res., April 1, 2007; 67(7): 3310 - 3319. [Abstract] [Full Text] [PDF]
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 S. Jesmin, S. Zaedi, N. Shimojo, M. Iemitsu, K. Masuzawa, N. Yamaguchi, C. N. Mowa, S. Maeda, Y. Hattori, and T. Miyauchi Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1030 - E1040. [Abstract] [Full Text] [PDF]
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S. H. L. George, M. Gertsenstein, K. Vintersten, E. Korets-Smith, J. Murphy, M. E. Stevens, J. J. Haigh, and A. Nagy Developmental and adult phenotyping directly from mutant embryonic stem cells PNAS, March 13, 2007; 104(11): 4455 - 4460. [Abstract] [Full Text] [PDF]
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 Y. Zhou, Y. Jiang, and Y. J. Kang A BRIEF COMMUNICATION: Copper Inhibition of Hydrogen Peroxide-Induced Hypertrophy in Embryonic Rat Cardiac H9c2 Cells Exp Biol Med, March 1, 2007; 232(3): 385 - 389. [Abstract] [Full Text] [PDF]
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N. Shraga-Heled, O. Kessler, C. Prahst, J. Kroll, H. Augustin, and G. Neufeld Neuropilin-1 and neuropilin-2 enhance VEGF121 stimulated signal transduction by the VEGFR-2 receptor FASEB J, March 1, 2007; 21(3): 915 - 926. [Abstract] [Full Text] [PDF]
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O. Caspi, A. Lesman, Y. Basevitch, A. Gepstein, G. Arbel, I. H. M. Habib, L. Gepstein, and S. Levenberg Tissue Engineering of Vascularized Cardiac Muscle From Human Embryonic Stem Cells Circ. Res., February 2, 2007; 100(2): 263 - 272. [Abstract] [Full Text] [PDF]
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A. Avivi, L. Brodsky, E. Nevo, and M. R. Band Differential expression profiling of the blind subterranean mole rat Spalax ehrenbergi superspecies: bioprospecting for hypoxia tolerance Physiol Genomics, January 12, 2007; 27(1): 54 - 64. [Abstract] [Full Text] [PDF]
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L. Piqueras, A. R. Reynolds, K. M. Hodivala-Dilke, A. Alfranca, J. M. Redondo, T. Hatae, T. Tanabe, T. D. Warner, and D. Bishop-Bailey Activation of PPAR{beta}/{delta} Induces Endothelial Cell Proliferation and Angiogenesis Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 63 - 69. [Abstract] [Full Text] [PDF]
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T.-H. Lee, S. Seng, H. Li, S. J. Kennel, H. K. Avraham, and S. Avraham Integrin Regulation by Vascular Endothelial Growth Factor in Human Brain Microvascular Endothelial Cells: ROLE OF {alpha}6beta1 INTEGRIN IN ANGIOGENESIS J. Biol. Chem., December 29, 2006; 281(52): 40450 - 40460. [Abstract] [Full Text] [PDF]
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T. Nomura, W.-C. Huang, H. E. Zhau, D. Wu, Z. Xie, H. Mimata, M. Zayzafoon, A. N. Young, F. F. Marshall, M. N. Weitzmann, et al. {beta}2-Microglobulin Promotes the Growth of Human Renal Cell Carcinoma through the Activation of the Protein Kinase A, Cyclic AMP-Responsive Element-Binding Protein, and Vascular Endothelial Growth Factor Axis Clin. Cancer Res., December 15, 2006; 12(24): 7294 - 7305. [Abstract] [Full Text] [PDF]
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W. Zhang, R. Swanson, Y. Xiong, B. Richard, and S. T. Olson Antiangiogenic Antithrombin Blocks the Heparan Sulfate-dependent Binding of Proangiogenic Growth Factors to Their Endothelial Cell Receptors: EVIDENCE FOR DIFFERENTIAL BINDING OF ANTIANGIOGENIC AND ANTICOAGULANT FORMS OF ANTITHROMBIN TO PROANGIOGENIC HEPARAN SULFATE DOMAINS J. Biol. Chem., December 8, 2006; 281(49): 37302 - 37310. [Abstract] [Full Text] [PDF]
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 A. de Paulis, N. Prevete, I. Fiorentino, F. W. Rossi, S. Staibano, N. Montuori, P. Ragno, A. Longobardi, B. Liccardo, A. Genovese, et al. Expression and Functions of the Vascular Endothelial Growth Factors and Their Receptors in Human Basophils J. Immunol., November 15, 2006; 177(10): 7322 - 7331. [Abstract] [Full Text] [PDF]
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N. Singh, P. D. Jani, T. Suthar, S. Amin, and B. K. Ambati Flt-1 Intraceptor Induces the Unfolded Protein Response, Apoptotic Factors, and Regression of Murine Injury-Induced Corneal Neovascularization Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4787 - 4793. [Abstract] [Full Text] [PDF]
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M. J. Bizzarro, N. Hussain, B. Jonsson, R. Feng, L. R. Ment, J. R. Gruen, H. Zhang, and V. Bhandari Genetic Susceptibility to Retinopathy of Prematurity Pediatrics, November 1, 2006; 118(5): 1858 - 1863. [Abstract] [Full Text] [PDF]
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 Q. Ke and M. Costa Hypoxia-Inducible Factor-1 (HIF-1) Mol. Pharmacol., November 1, 2006; 70(5): 1469 - 1480. [Abstract] [Full Text] [PDF]
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H. Xu, L. Zeng, H. Peng, S. Chen, J. Jones, T.-L. Chew, M. M. Sadeghi, Y. S. Kanwar, and F. R. Danesh HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced "inside-out" signaling to extracellular matrix by preventing RhoA activation Am J Physiol Renal Physiol, November 1, 2006; 291(5): F995 - F1004. [Abstract] [Full Text] [PDF]
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L. Poliseno, A. Tuccoli, L. Mariani, M. Evangelista, L. Citti, K. Woods, A. Mercatanti, S. Hammond, and G. Rainaldi MicroRNAs modulate the angiogenic properties of HUVECs Blood, November 1, 2006; 108(9): 3068 - 3071. [Abstract] [Full Text] [PDF]
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W.-U. Kim, S. S. Kang, S.-A. Yoo, K.-H. Hong, D.-G. Bae, M.-S. Lee, S. W. Hong, C.-B. Chae, and C.-S. Cho Interaction of Vascular Endothelial Growth Factor 165 with Neuropilin-1 Protects Rheumatoid Synoviocytes from Apoptotic Death by Regulating Bcl-2 Expression and Bax Translocation J. Immunol., October 15, 2006; 177(8): 5727 - 5735. [Abstract] [Full Text] [PDF]
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 H. R. Lijnen, V. Christiaens, I. Scroyen, G. Voros, M. Tjwa, P. Carmeliet, and D. Collen Impaired adipose tissue development in mice with inactivation of placental growth factor function. Diabetes, October 1, 2006; 55(10): 2698 - 2704. [Abstract] [Full Text] [PDF]
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