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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-12-3793. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3793v1 102/1/161    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 Xia, Y.-P. Articles by Rudge, J. S. Search for Related Content PubMed PubMed Citation Articles by Xia, Y.-P. Articles by Rudge, J. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 161-168 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis Yu-Ping Xia, Baosheng Li, Donna Hylton, Michael Detmar, George D. Yancopoulos, and John S. Rudge From Regeneron Pharmaceuticals, Tarrytown, NY; and Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown. Gene therapy approaches involving vascular endothelial growth factor (VEGF) to promote therapeutic angiogenesis are under consideration for conditions ranging from ischemic heart disease to nonhealing skin ulcers. Here we make the surprising observation that the transgenic delivery of VEGF to the skin results in a profound inflammatory skin condition with many of the cellular and molecular features of psoriasis, including the characteristic vascular changes, epidermal alterations, and inflammatory infiltrates. Even longstanding psoriatic disease remains dependent on the transgenic VEGF in this model because it can be effectively reversed by the addition of VEGF Trap, a potent VEGF antagonist. Previous attempts to faithfully replicate the psoriatic phenotype through the transgenic delivery of epidermal keratinocyte growth factors or inflammatory mediators generated phenotypes with only partial resemblance to human psoriasis, leaving unanswered questions about the etiology of this disease. The ability of transgenic VEGF to induce a psoriasiform phenotype suggests a new etiology and treatment approach for this disease and further substantiates emerging concerns about possible proinflammatory adverse effects that might be associated with therapeutic attempts to deliver VEGF. (Blood. 2003;102:161-168) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Xiong, Y. Huo, C. Chen, H. Zeng, X. Lu, C. Wei, C. Ruan, X. Zhang, Z. Hu, M. Shibuya, et al. Vascular Endothelial Growth Factor (VEGF) Receptor-2 Tyrosine 1175 Signaling Controls VEGF-induced von Willebrand Factor Release from Endothelial Cells via Phospholipase C-{gamma}1- and Protein Kinase A-dependent Pathways J. Biol. Chem., August 28, 2009; 284(35): 23217 - 23224. [Abstract] [Full Text] [PDF] R. P. Kataru, K. Jung, C. Jang, H. Yang, R. A. Schwendener, J. E. Baik, S. H. Han, K. Alitalo, and G. Y. 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Epidermal Vascular Endothelial Growth Factor Production Is Required for Permeability Barrier Homeostasis, Dermal Angiogenesis, and the Development of Epidermal Hyperplasia: Implications for the Pathogenesis of Psoriasis Am. J. Pathol., September 1, 2008; 173(3): 689 - 699. [Abstract] [Full Text] [PDF] H. Hvid, I. Teige, P. H. Kvist, L. Svensson, and K. Kemp TPA induction leads to a Th17-like response in transgenic K14/VEGF mice: a novel in vivo screening model of psoriasis Int. Immunol., August 1, 2008; 20(8): 1097 - 1106. [Abstract] [Full Text] [PDF] D. M. Danilenko Review Paper: Preclinical Models of Psoriasis Vet. Pathol., July 1, 2008; 45(4): 563 - 575. [Abstract] [Full Text] [PDF] C. Halin, H. Fahrngruber, J. G. Meingassner, G. Bold, A. Littlewood-Evans, A. Stuetz, and M. Detmar Inhibition of Chronic and Acute Skin Inflammation by Treatment with a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Am. J. Pathol., July 1, 2008; 173(1): 265 - 277. 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