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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.
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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.

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