Copyright © 2004, European Society of Cardiology
The biology of vascular endothelial growth factors
aMolecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8) University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland
* Corresponding author. Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), 00014 University of Helsinki, Finland. Tel.: +358 9 1912 5537; fax: +358 9 1912 5510. Email address: Karri.Paavonen{at}Helsinki.Fi
The discovery of the vascular endothelial growth factor (VEGF) family members VEGF, VEGF-B, placental growth factor (PlGF), VEGF-C and VEGF-D and their receptors VEGFR-1, -2 and -3 has provided tools for studying the vascular system in development as well as in diseases ranging from ischemic heart disease to cancer. VEGF has been established as the prime angiogenic molecule during development, adult physiology and pathology. PlGF may primarily mediate arteriogenesis, the formation of collateral arteries from preexisting arterioles, with potential future therapeutic use in for example occlusive atherosclerotic disease. VEGF-C and VEGF-D are primarily lymphangiogenic factors, but they can also induce angiogenesis in some conditions. While many studies have addressed the role of angiogenesis and the blood vasculature in human physiology, the lymphatic vascular system has until recently attracted very little attention. In this review, we will discuss recent advances in angiogenesis research and provide an overview of the molecular players involved in lymphangiogenesis.
KEYWORDS Angiogenesis; Lymphangiogenesis; Growth factors; Endothelial receptors; VEGF
Time for primary review 18 days
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 A. Ny, M. Koch, W. Vandevelde, M. Schneider, C. Fischer, A. Diez-Juan, E. Neven, I. Geudens, S. Maity, L. Moons, et al. Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles Blood, September 1, 2008; 112(5): 1740 - 1749. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
E. V. Yang, A. K. Sood, M. Chen, Y. Li, T. D. Eubank, C. B. Marsh, S. Jewell, N. A. Flavahan, C. Morrison, P.-E. Yeh, et al. Norepinephrine Up-regulates the Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase (MMP)-2, and MMP-9 in Nasopharyngeal Carcinoma Tumor Cells Cancer Res., November 1, 2006; 66(21): 10357 - 10364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 R.A. Goodlad, A.J. Ryan, S.R. Wedge, I.T. Pyrah, D. Alferez, R. Poulsom, N.R. Smith, N. Mandir, A.J. Watkins, and R.W. Wilkinson Inhibiting vascular endothelial growth factor receptor-2 signaling reduces tumor burden in the ApcMin/+ mouse model of early intestinal cancer Carcinogenesis, October 1, 2006; 27(10): 2133 - 2139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Lash, B. Schiessl, M. Kirkley, B. A. Innes, A. Cooper, R. F. Searle, S. C. Robson, and J. N. Bulmer Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy J. Leukoc. Biol., September 1, 2006; 80(3): 572 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. F. Yang, R. T.P. Poon, Y. Liu, C. K. Lau, D. W. Ho, K. H. Tam, C. T. Lam, and S. T. Fan High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis. Mol. Cancer Ther., September 1, 2006; 5(9): 2261 - 2270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 S. E. Holloway, A. W. Beck, L. Shivakumar, J. Shih, J. B. Fleming, and R. A. Brekken Selective Blockade of Vascular Endothelial Growth Factor Receptor 2 With an Antibody Against Tumor-Derived Vascular Endothelial Growth Factor Controls the Growth of Human Pancreatic Adenocarcinoma Xenografts Ann. Surg. Oncol., August 1, 2006; 13(8): 1145 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
V. Bhandari, R. Choo-Wing, S. P. Chapoval, C. G. Lee, C. Tang, Y. K. Kim, B. Ma, P. Baluk, M. I. Lin, D. M. McDonald, et al. Essential role of nitric oxide in VEGF-induced, asthma-like angiogenic, inflammatory, mucus, and physiologic responses in the lung PNAS, July 18, 2006; 103(29): 11021 - 11026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dome, J. Timar, J. Dobos, L. Meszaros, E. Raso, S. Paku, I. Kenessey, G. Ostoros, M. Magyar, A. Ladanyi, et al. Identification and clinical significance of circulating endothelial progenitor cells in human non-small cell lung cancer. Cancer Res., July 15, 2006; 66(14): 7341 - 7347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pieren, A. E. Prota, C. Ruch, D. Kostrewa, A. Wagner, K. Biedermann, F. K. Winkler, and K. Ballmer-Hofer Crystal Structure of the Orf Virus NZ2 Variant of Vascular Endothelial Growth Factor-E: IMPLICATIONS FOR RECEPTOR SPECIFICITY J. Biol. Chem., July 14, 2006; 281(28): 19578 - 19587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kivela, M. Silvennoinen, A.-M. Touvra, T. M. Lehti, H. Kainulainen, and V. Vihko Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle FASEB J, July 1, 2006; 20(9): 1570 - 1572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Biswas, S. Canosa, D. Schoenfeld, J. Schoenfeld, P. Li, L. C. Cheas, J. Zhang, A. Cordova, B. Sumpio, and J. A. Madri PECAM-1 Affects GSK-3{beta}-Mediated {beta}-Catenin Phosphorylation and Degradation Am. J. Pathol., July 1, 2006; 169(1): 314 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jones-Bolin, H. Zhao, K. Hunter, A. Klein-Szanto, and B. Ruggeri The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice. Mol. Cancer Ther., July 1, 2006; 5(7): 1744 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Lavine, A. C. White, C. Park, C. S. Smith, K. Choi, F. Long, C.-c. Hui, and D. M. Ornitz Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes & Dev., June 15, 2006; 20(12): 1651 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Piper and E. A. Martinson Cardiovascular Research speeds up-Even more Cardiovasc Res, March 1, 2006; 69(4): 773 - 776. [Full Text] [PDF]
|
|
|
|
|
|
W. Fureder, M.-T. Krauth, W. R. Sperr, K. Sonneck, I. Simonitsch-Klupp, L. Mullauer, M. Willmann, H.-P. Horny, and P. Valent Evaluation of Angiogenesis and Vascular Endothelial Growth Factor Expression in the Bone Marrow of Patients with Aplastic Anemia Am. J. Pathol., January 1, 2006; 168(1): 123 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Lee, M. D. Canny, A. De Erkenez, D. Krilleke, Y.-S. Ng, D. T. Shima, A. Pardi, and F. Jucker A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165 PNAS, December 27, 2005; 102(52): 18902 - 18907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wagner, K.-D. Wagner, H. Theres, C. Englert, A. Schedl, and H. Scholz Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1 Genes & Dev., November 1, 2005; 19(21): 2631 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Mould, S. A. Greco, M. M. Cahill, I. D. Tonks, D. Bellomo, C. Patterson, A. Zournazi, A. Nash, P. Scotney, N. K. Hayward, et al. Transgenic Overexpression of Vascular Endothelial Growth Factor-B Isoforms by Endothelial Cells Potentiates Postnatal Vessel Growth In Vivo and In Vitro Circ. Res., September 16, 2005; 97(6): e60 - e70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Hewett, L. W. Norman, D. Sedmera, R. J. Barker, C. Justus, J. Zhang, S. W. Kubalak, and R. G. Gourdie Knockout of the neural and heart expressed gene HF-1b results in apical deficits of ventricular structure and activation Cardiovasc Res, August 15, 2005; 67(3): 548 - 560. [Abstract] [Full Text] [PDF]
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|
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S. M. Muller, G. Terszowski, C. Blum, C. Haller, V. Anquez, S. Kuschert, P. Carmeliet, H. G. Augustin, and H.-R. Rodewald Gene targeting of VEGF-A in thymus epithelium disrupts thymus blood vessel architecture PNAS, July 26, 2005; 102(30): 10587 - 10592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Carpenter, Y. Lin, S. Stoll, R. L. Raffai, R. McCuskey, and R. Wang VEGF is crucial for the hepatic vascular development required for lipoprotein uptake Development, July 15, 2005; 132(14): 3293 - 3303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Post and J. Waltenberger Modulation of growth factor action in the cardiovascular system Cardiovasc Res, February 15, 2005; 65(3): 547 - 549. [Full Text] [PDF]
|
|