SEARCH:   Advanced

Blood, 1 April 2006, Vol. 107, No. 7, pp. 2705-2712. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-09-3541. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3541v1 107/7/2705    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Calvani, M. Articles by Melillo, G. Search for Related Content PubMed PubMed Citation Articles by Calvani, M. Articles by Melillo, G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Hypoxic induction of an HIF-1–dependent bFGF autocrine loop drives angiogenesis in human endothelial cells Maura Calvani, Annamaria Rapisarda, Badarch Uranchimeg, Robert H. Shoemaker, and Giovanni Melillo From the Developmental Therapeutics Program, Science Applications International Corporation-Frederick, National Cancer Institute at Frederick, MD. Hypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells, the transcriptional response to oxygen deprivation is largely mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1 and HIF-1 subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF- subunits in this process are still poorly understood. We show that human umbilical vein endothelial cells (HUVECs) cultured in the absence of growth factors survive and form tubelike structures when cultured under hypoxic, but not normoxic, conditions. HUVECs expressed both HIF-1 and HIF-2 when cultured under hypoxic conditions. Transfection of HIF-1, but not HIF-2, siRNA to HUVECs completely abrogated hypoxic induction of cords. Neutralizing antibodies to bFGF, but not IGF-1, VEGF, or PDGF-BB, blocked survival and sprouting of HUVECs under hypoxic conditions, suggesting the existence of an autocrine loop induced by low oxygen levels. Notably, bFGF-dependent induction of cord formation under normoxic conditions required HIF-1 activity, which was also essential for hypoxic induction of bFGF mRNA and protein expression. These results uncover the existence of an HIF-1–bFGF amplification pathway that mediates survival and sprouting of endothelial cells under hypoxic conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Martorell, M. Gentile, J. Rius, C. Rodriguez, J. Crespo, L. Badimon, and J. Martinez-Gonzalez The Hypoxia-Inducible Factor 1/NOR-1 Axis Regulates the Survival Response of Endothelial Cells to Hypoxia Mol. Cell. Biol., November 1, 2009; 29(21): 5828 - 5842. [Abstract] [Full Text] [PDF] C. K. Lau, Z. F. Yang, D. W. Ho, M. N. Ng, G. C.T. Yeoh, R. T.P. Poon, and S. T. Fan An Akt/Hypoxia-Inducible Factor-1{alpha}/Platelet-Derived Growth Factor-BB Autocrine Loop Mediates Hypoxia-Induced Chemoresistance in Liver Cancer Cells and Tumorigenic Hepatic Progenitor Cells Clin. Cancer Res., May 15, 2009; 15(10): 3462 - 3471. [Abstract] [Full Text] [PDF] T. Zhao, D. Wang, S. Y. Cheranov, M. Karpurapu, K. R. Chava, V. Kundumani-Sridharan, D. A. Johnson, J. S. Penn, and G. N. Rao A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis J. Lipid Res., March 1, 2009; 50(3): 521 - 533. [Abstract] [Full Text] [PDF] J.-O. Moon, T. P. Welch, F. J. Gonzalez, and B. L. Copple Reduced liver fibrosis in hypoxia-inducible factor-1{alpha}-deficient mice Am J Physiol Gastrointest Liver Physiol, March 1, 2009; 296(3): G582 - G592. [Abstract] [Full Text] [PDF] L. M. Greenberger, I. D. Horak, D. Filpula, P. Sapra, M. Westergaard, H. F. Frydenlund, C. Albaek, H. Schroder, and H. Orum A RNA antagonist of hypoxia-inducible factor-1{alpha}, EZN-2968, inhibits tumor cell growth Mol. Cancer Ther., November 1, 2008; 7(11): 3598 - 3608. [Abstract] [Full Text] [PDF] D. Bae, S. Lu, C. A. Taglienti, and A. M. Mercurio Metabolic Stress Induces the Lysosomal Degradation of Neuropilin-1 but Not Neuropilin-2 J. Biol. Chem., October 17, 2008; 283(42): 28074 - 28080. [Abstract] [Full Text] [PDF] G. Cheng, H. Zhang, X. Yang, E. Tzima, K. L. Ewalt, P. Schimmel, and J. E. Faber Effect of mini-tyrosyl-tRNA synthetase on ischemic angiogenesis, leukocyte recruitment, and vascular permeability Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1138 - R1146. [Abstract] [Full Text] [PDF] S. Y. Cheranov, M. Karpurapu, D. Wang, B. Zhang, R. C. Venema, and G. N. Rao An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis Blood, June 15, 2008; 111(12): 5581 - 5591. [Abstract] [Full Text] [PDF] M. Calvani, D. Trisciuoglio, C. Bergamaschi, R. H. Shoemaker, and G. Melillo Differential Involvement of Vascular Endothelial Growth Factor in the Survival of Hypoxic Colon Cancer Cells Cancer Res., January 1, 2008; 68(1): 285 - 291. [Abstract] [Full Text] [PDF] S. M. Black, J. M. DeVol, and S. Wedgwood Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation Am J Physiol Cell Physiol, January 1, 2008; 294(1): C345 - C354. [Abstract] [Full Text] [PDF] M. Bosch-Marce, H. Okuyama, J. B. Wesley, K. Sarkar, H. Kimura, Y. V. Liu, H. Zhang, M. Strazza, S. Rey, L. Savino, et al. Effects of Aging and Hypoxia-Inducible Factor-1 Activity on Angiogenic Cell Mobilization and Recovery of Perfusion After Limb Ischemia Circ. Res., December 7, 2007; 101(12): 1310 - 1318. [Abstract] [Full Text] [PDF] A. K. Bajpai, E. Blaskova, S. B. Pakala, T. Zhao, W. C. Glasgow, J. S. Penn, D. A. Johnson, and G. N. Rao 15(S)-HETE Production in Human Retinal Microvascular Endothelial Cells by Hypoxia: Novel Role for MEK1 in 15(S)-HETE Induced Angiogenesis Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 4930 - 4938. [Abstract] [Full Text] [PDF] G. L. Semenza Regulation of tissue perfusion in mammals by hypoxia-inducible factor 1 Exp Physiol, November 1, 2007; 92(6): 988 - 991. [Abstract] [Full Text] [PDF] M. Egger, W. Schgoer, A. G. E. Beer, J. Jeschke, J. Leierer, M. Theurl, S. Frauscher, O. M. Tepper, A. Niederwanger, A. Ritsch, et al. Hypoxia up-regulates the angiogenic cytokine secretoneurin via an HIF-1{alpha}- and basic FGF-dependent pathway in muscle cells FASEB J, September 1, 2007; 21(11): 2906 - 2917. [Abstract] [Full Text] [PDF] K. Shchors and G. Evan Tumor Angiogenesis: Cause or Consequence of Cancer? Cancer Res., August 1, 2007; 67(15): 7059 - 7061. [Abstract] [Full Text] [PDF] L. Veschini, D. Belloni, C. Foglieni, M. G. Cangi, M. Ferrarini, F. Caligaris-Cappio, and E. Ferrero Hypoxia-inducible transcription factor-1 alpha determines sensitivity of endothelial cells to the proteosome inhibitor bortezomib Blood, March 15, 2007; 109(6): 2565 - 2570. [Abstract] [Full Text] [PDF] H. Tanaka, M. Yamamoto, N. Hashimoto, M. Miyakoshi, S. Tamakawa, M. Yoshie, Y. Tokusashi, K. Yokoyama, Y. Yaginuma, and K. Ogawa Hypoxia-Independent Overexpression of Hypoxia-Inducible Factor 1{alpha} as an Early Change in Mouse Hepatocarcinogenesis Cancer Res., December 1, 2006; 66(23): 11263 - 11270. [Abstract] [Full Text] [PDF] A. Naldini, D. Leali, A. Pucci, E. Morena, F. Carraro, B. Nico, D. Ribatti, and M. Presta Cutting Edge: IL-1beta Mediates the Proangiogenic Activity of Osteopontin-Activated Human Monocytes J. Immunol., October 1, 2006; 177(7): 4267 - 4270. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020