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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5581-5591. Prepublished online as a Blood First Edition Paper on April 11, 2008; DOI 10.1182/blood-2007-11-126680. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-126680v1 111/12/5581    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 Cheranov, S. Y. Articles by Rao, G. N. Search for Related Content PubMed PubMed Citation Articles by Cheranov, S. Y. Articles by Rao, G. N. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY An essential role for SRC-activated STAT-3 in 14,15-EET–induced VEGF expression and angiogenesis Sergey Y. Cheranov1,*, Manjula Karpurapu1,*, Dong Wang1, Baolin Zhang1, Richard C. Venema2, and Gadiparthi N. Rao1 1 Department of Physiology, University of Tennessee Health Science Center, Memphis; and 2 Department of Pediatrics, Medical College of Georgia, Augusta To understand the molecular mechanisms underlying 14,15-epoxyeicosatrienoic acid (14,15-EET)–induced angiogenesis, here we have studied the role of signal transducer and activator of transcription-3 (STAT-3). 14,15-EET stimulated the tyrosine phosphorylation of STAT-3 and its translocation from the cytoplasm to the nucleus in human dermal microvascular endothelial cells (HDMVECs). Adenovirus-mediated delivery of dominant negative STAT-3 substantially inhibited 14,15-EET–induced HDMVEC migration, and tube formation and Matrigel plug angiogenesis. 14,15-EET activated Src, as measured by its tyrosine phosphorylation and blockade of its activation by adenovirus-mediated expression of its dominant negative mutant, significantly attenuated 14,15-EET–induced STAT-3 phosphorylation in HDMVECs and the migration and tube formation of these cells and Matrigel plug angiogenesis. 14,15-EET induced the expression of vascular endothelial cell growth factor (VEGF) in a time- and Src-STAT-3–dependent manner in HDMVECs. Transfac analysis of VEGF promoter revealed the presence of STAT-binding elements and 14,15-EET induced STAT-3 binding to this promoter in vivo, and this interaction was inhibited by suppression of Src-STAT-3 signaling. Neutralizing anti-VEGF antibodies completely blocked 14,15-EET–induced HDMVEC migration and tube formation and Matrigel plug angiogenesis. These results reveal that Src-dependent STAT-3–mediated VEGF expression is a major mechanism of 14,15-EET–induced angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. S. K. Potula, D. Wang, D. Van Quyen, N. K. Singh, V. Kundumani-Sridharan, M. Karpurapu, E. A. Park, W. C. Glasgow, and G. N. Rao Src-dependent STAT-3-mediated Expression of Monocyte Chemoattractant Protein-1 Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-induced Vascular Smooth Muscle Cell Migration J. Biol. Chem., November 6, 2009; 284(45): 31142 - 31155. [Abstract] [Full Text] [PDF] S. Y. Cheranov, D. Wang, V. Kundumani-Sridharan, M. Karpurapu, Q. Zhang, K. R. Chava, and G. N. Rao The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B-dependent expression of interleukin-8 Blood, June 4, 2009; 113(23): 6023 - 6033. [Abstract] [Full Text] [PDF] A. A. Spector Arachidonic acid cytochrome P450 epoxygenase pathway J. Lipid Res., April 1, 2009; 50(Supplement): S52 - S56. [Abstract] [Full Text] [PDF]

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