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Blood, 15 January 2006, Vol. 107, No. 2, pp. 584-590. Prepublished online as a Blood First Edition Paper on September 27, 2005; DOI 10.1182/blood-2005-07-3033. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-3033v1 107/2/584    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 Licht, A. H. Articles by Breier, G. Search for Related Content PubMed PubMed Citation Articles by Licht, A. H. Articles by Breier, G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Inhibition of hypoxia-inducible factor activity in endothelial cells disrupts embryonic cardiovascular development Alexander H. Licht, Felix Müller-Holtkamp, Ingo Flamme, and Georg Breier From the Department of Pathology, Faculty of Medicine, University of Technology, Dresden, Germany; Department of Molecular Cell Biology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and Bayer Health Care, Wuppertal, Germany. Hypoxia-inducible factors (HIFs) are transcriptional regulators that mediate the cellular response to low oxygen levels. By stimulating the expression of angiogenic growth factors such as vascular endothelial growth factor (VEGF), they trigger the neovascularization of tissues under physiologic and pathologic conditions. Here, we have investigated the endothelial cell–autonomous HIF function in blood vessel growth and development by expressing a dominant-negative HIF mutant (HIFdn) that inhibits the transcriptional responses mediated by both HIF-1 and HIF-2, specifically in endothelial cells of transgenic mice. HIFdn transgenic embryos were growth retarded and died around E11.5. Primitive vascular networks were established, but vascular remodeling in the yolk sac and in the embryo proper was defective, and vascular sprouts failed to invade the neuroepithelium. In addition, heart looping was incomplete, and the ventricles of the heart were thin-walled and lacked trabeculation. Similar cardiovascular defects have been observed in Tie2–deficient mouse embryos. Consistently, HIFdn transgenic embryos expressed reduced levels of the endothelial angiopoietin receptor, Tie-2, whereas other endothelial markers, such as PECAM-1, Tie-1, and VE-cadherin were not affected. These results show that HIFs in endothelial cells are essential for embryonic heart and blood vessel development and control angiogenesis and vascular remodeling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: EC does it with HIF Gregg L. Semenza Blood 2006 107: 419-420. [Full Text] [PDF] This article has been cited by other articles: Y. V. Liu, M. E. Hubbi, F. Pan, K. R. McDonald, M. Mansharamani, R. N. Cole, J. O. Liu, and G. L. Semenza Calcineurin Promotes Hypoxia-inducible Factor 1{alpha} Expression by Dephosphorylating RACK1 and Blocking RACK1 Dimerization J. Biol. Chem., December 21, 2007; 282(51): 37064 - 37073. [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] T. G. Nacak, A. Alajati, K. Leptien, C. Fulda, H. Weber, T. Miki, F. S. Czepluch, J. Waltenberger, T. Wieland, H. G. Augustin, et al. The BTB-Kelch Protein KLEIP Controls Endothelial Migration and Sprouting Angiogenesis Circ. Res., April 27, 2007; 100(8): 1155 - 1163. [Abstract] [Full Text] [PDF] I. Kojima, T. Tanaka, R. Inagi, H. Kato, T. Yamashita, A. Sakiyama, O. Ohneda, N. Takeda, M. Sata, T. Miyata, et al. Protective Role of Hypoxia-Inducible Factor-2{alpha} against Ischemic Damage and Oxidative Stress in the Kidney J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1218 - 1226. [Abstract] [Full Text] [PDF] P. A. Carroll, H. L. Kenerson, R. S. Yeung, and M. Lagunoff Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells Activates Hypoxia-Induced Factors J. Virol., November 1, 2006; 80(21): 10802 - 10812. [Abstract] [Full Text] [PDF]

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