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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2440-2448. Prepublished online as a Blood First Edition Paper on May 29, 2007; DOI 10.1182/blood-2007-03-078709. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-03-078709v1 110/7/2440    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 Deregibus, M. C. Articles by Camussi, G. Search for Related Content PubMed PubMed Citation Articles by Deregibus, M. C. Articles by Camussi, G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Endothelial progenitor cell–derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA Maria Chiara Deregibus1, Vincenzo Cantaluppi1, Raffaele Calogero2, Marco Lo Iacono2, Ciro Tetta3, Luigi Biancone1, Stefania Bruno1, Benedetta Bussolati1, and Giovanni Camussi1 1 Department of Internal Medicine, Research Center for Experimental Medicine (CeRMS) and Center for Molecular Biotechnology, Torino, Italy; 2 Department of Clinical and Biologic Sciences, University of Torino, Torino, Italy; 3 Fresenius Medical Care, Bad Homburg, Germany Membrane-derived microvesicles (MVs) are released from the cell surface and are implicated in cell-to-cell communication. We evaluated whether MVs derived from endothelial progenitor cells (EPCs) are able to trigger angiogenesis. We found that EPC-derived MVs were incorporated in endothelial cells by interaction with 4 and ß1 integrins expressed on the MV surface. In vitro, MVs promoted endothelial cell survival, proliferation, and organization in capillary-like structures. In vivo, in severe combined immunodeficient (SCID) mice, MV-stimulated human endothelial cells organized in patent vessels. When incubated with RNase, despite their internalization into endothelial cells, MVs failed to induce in vitro and in vivo angiogenic effects. mRNA transfer was shown by transduction of GFP protein in endothelial cells by MVs containing GFP-mRNA and the biologic relevance by the angiogenic effect of MV-mRNA extract delivered by lipofectamine. Microarray ana-lysis and quantitative reverse transcription–polymerase chain reaction (RT-PCR) of MV-mRNA extract indicated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated with the PI3K/AKT signaling pathway. Protein expression and functional studies showed that PI3K and eNOS play a critical role in the angiogenic effect of MVs. These results suggest that EPCs may activate angiogenesis in endothelial cells by releasing MVs able to trigger an angiogenic program. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Trading places: mRNA transfer between cells Andrew S. Weyrich, Larry W. Kraiss, and Guy A. Zimmerman Blood 2007 110: 2219. [Full Text] [PDF] This article has been cited by other articles: T. W. Wakefield, D. D. Myers, and P. K. Henke Mechanisms of Venous Thrombosis and Resolution Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 387 - 391. [Abstract] [Full Text] [PDF]

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