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Blood, 1 January 2005, Vol. 105, No. 1, pp. 207-214. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-04-1519. This Article Full Text (PDF) All Versions of this Article: 2004-04-1519v1 105/1/207    most recent Alert me when this article is cited Alert me if a correction is posted 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 Matsushita, K. Articles by Lowenstein, C. J Search for Related Content PubMed PubMed Citation Articles by Matsushita, K. Articles by Lowenstein, C. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 21, 2004 Accepted August 23, 2004 Vascular endothelial growth factor regulation of Weibel-Palade body exocytosis Kenji Matsushita, Munekazu Yamakuchi, Craig N Morrell, Michitaka Ozaki, Brian O'Rourke, Kaikobad Irani, and Charles J Lowenstein* Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA * Corresponding author; email: clowenst{at}jhmi.edu. Vascular endothelial growth factor (VEGF) not only regulates angiogenesis, vascular permeability, and vasodilation, but also promotes vascular inflammation. However, the molecular basis for the pro-inflammatory effects of VEGF is not understood. We now show that VEGF activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. VEGF triggers endothelial exocytosis in part through calcium and phospholipase C- (PLC-) signal transduction. However, VEGF also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase (eNOS) production of nitric oxide (NO) which nitrosylates N-ethylmaleimide sensitive factor (NSF) and inhibits exocytosis. Thus VEGF plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the pro-inflammatory effects of VEGF. 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] S. Fischer, M. Nishio, S. C. Peters, M. Tschernatsch, M. Walberer, S. Weidemann, R. Heidenreich, P. O. Couraud, B. B. Weksler, I. A. Romero, et al. Signaling mechanism of extracellular RNA in endothelial cells FASEB J, July 1, 2009; 23(7): 2100 - 2109. [Abstract] [Full Text] [PDF] M.-C. Kuo, D. Patschan, S. Patschan, L. Cohen-Gould, H.-C. Park, J. Ni, F. Addabbo, and M. S. Goligorsky Ischemia-Induced Exocytosis of Weibel-Palade Bodies Mobilizes Stem Cells J. 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Wagner Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin Blood, October 1, 2005; 106(7): 2334 - 2339. [Abstract] [Full Text] [PDF] M. Yamakuchi, J. J.M. Greer, S. J. Cameron, K. Matsushita, C. N. Morrell, K. Talbot-Fox, W. M. Baldwin III, D. J. Lefer, and C. J. Lowenstein HMG-CoA Reductase Inhibitors Inhibit Endothelial Exocytosis and Decrease Myocardial Infarct Size Circ. Res., June 10, 2005; 96(11): 1185 - 1192. [Abstract] [Full Text] [PDF]

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