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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, 2007June 18, 2007; DOI 10.1182/blood-2006-08-040691. This Article 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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 9, 2006 Accepted June 7, 2007 Extracellular RNA mediates endothelial cell permeability via vascular endothelial growth factor Silvia Fischer, Tibo Gerriets, Carina Wessels, Maureen Walberer, Sawa Kostin, Erwin Stolz, Kirila Zheleva, Andreas Hocke, Stefan Hippenstiel, and Klaus T. Preissner* Department of Anesthesiology, Kerckhoff-Clinic, Bad Nauheim, Germany Radiology-Department of Experimental Neurology, Kerckhoff-Clinic, Bad Nauheim, Germany Department of Neurology, Medical School, Justus-Liebig University, Giessen, Germany Core Lab for Molecular and Structural Biology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany Dept of Internal Medicine/Infectious & Pulmonary Diseases, Charite'-Universitatsmedizin, Berlin, Germany Department of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany * Corresponding author; email: klaus.t.preissner{at}biochemie.med.uni-giessen.de. 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 superior sagittal sinus 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?

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