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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2457-2465. Prepublished online as a Blood First Edition Paper on June 19, 2007; DOI 10.1182/blood-2006-08-040691. This Article Full Text Full Text (PDF) Supplemental Methods and Tables Supplemental Figures All Versions of this Article: blood-2006-08-040691v1 blood-2006-08-040691v2 110/7/2457    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 Fischer, S. Articles by Preissner, K. T. Search for Related Content PubMed PubMed Citation Articles by Fischer, S. Articles by Preissner, K. T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Extracellular RNA mediates endothelial-cell permeability via vascular endothelial growth factor Silvia Fischer1,2, Tibo Gerriets3,4, Carina Wessels3, Maureen Walberer3,4, Sawa Kostin5, Erwin Stolz3,4, Kirila Zheleva1, Andreas Hocke6, Stefan Hippenstiel6, and Klaus T. Preissner1 1 Department of Biochemistry Medical School, Justus-Liebig-University, Giessen; 2 Department of Anesthesiology, Department of Experimental Neurology, Kerckhoff-Klinik, Bad Nauheim; 3 Department of Neurology, Medical School, Justus-Liebig-University, Giessen; 4 Department of Radiology, Department of Experimental Neurology, Kerckhoff-Klinik, Bad Nauheim; 5 Core Lab for Molecular and Structural Biology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim; 6 Charité–Universitätsmedizin, Department of Internal Medicine/Infectious Pulmonary Diseases, Berlin, Germany Cell injury leads to exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage. Here, we demonstrate that natural extracellular RNA as well as artificial RNA (poly-I:C), or single-stranded RNA but not DNA, significantly increased the permeability across brain microvascular endothelial cells in vitro and in vivo. RNA-induced hyperpermeability of tight monolayers of endothelial cells correlated with disintegration of tight junctions and was mediated through vascular endothelial growth factor (VEGF), reminiscent of heparin's activities. Antisense oligonucleotides against VEGF-receptor 2 (VEGF-R2) prevented the permeability-inducing activity of extracellular RNA and heparin completely. Hence, these polyanionic substances can lead to mobilization/stabilization of VEGF with the subsequent activation of VEGF-R2. In accordance with these functional data, strong binding of VEGF as well as other growth factors to RNA was demonstrable. In in vivo rat models of FeCl3-induced sinus sagittal is superior thrombosis and stroke/brain edema, pretreatment of animals with RNase (but not DNase) resulted in a significant reduction of vessel occlusion, infarct volume, and prevention of brain edema formation. Together, these results identify extracellular RNA as a novel natural permeability factor, upstream of VEGF, whereas counteracting RNase treatment may serve as new vessel-protective modality. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. VANDENBROUCKE, D. MEHTA, R. MINSHALL, and A. B. MALIK Regulation of Endothelial Junctional Permeability Ann. N.Y. Acad. Sci., March 1, 2008; 1123(1): 134 - 145. [Abstract] [Full Text] [PDF]

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