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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 8, 2007 Accepted May 25, 2007 Endothelial progenitor cell-derived microvesicles activate an angiogenic program in endothelial cells by an horizontal transfer of mRNA Maria Chiara Deregibus, Vincenzo Cantaluppi, Raffaele Calogero, Marco Lo Iacono, Ciro Tetta, Luigi Biancone, Stefania Bruno, Benedetta Bussolati, and Giovanni Camussi* Department of Internal Medicine, (CeRMS) and Center for Molecular Biotechnology, University of Torino, Torino, Italy Department of Clinical and Biological Sciences, University of Torino, Torino, Italy Fresenius Medical Care, Bad Homburg, Germany * Corresponding author; email: giovanni.camussi{at}unito.it. Membrane-derived microvesicles (MVs) are released from cell surface and are implicated in cell to cell communication. We here evaluated whether MVs derived from endothelial progenitor cells (EPC) are able to trigger angiogenesis. We found that EPC-derived MVs were incorporated in endothelial cells by interaction with 4- and 1-integrins expressed on MV surface. In vitro, MVs promoted endothelial cell survival, proliferation and organization in capillary-like structures. In vivo, in 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 demonstrated by transduction of GFP protein in endothelial cells by MVs containing GFP-mRNA and the biological relevance by the angiogenic effect of MV-mRNA-extract delivered by lipofectamine. Microarray analysis and quantitative 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 signalling pathway. Protein expression and functional studies demonstrated that PI3K and eNOS play a critical role in the angiogenic effect of MVs. These results suggest that EPC 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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