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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1868-1876. Prepublished online as a Blood First Edition Paper on May 23, 2006; DOI 10.1182/blood-2006-04-014175. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-04-014175v1 108/6/1868    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 Sapet, C. Articles by Anfosso, F. Search for Related Content PubMed PubMed Citation Articles by Sapet, C. Articles by Anfosso, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2 Cédric Sapet, Stéphanie Simoncini, Béatrice Loriod, Denis Puthier, José Sampol, Catherine Nguyen, Françoise Dignat-George, and Francine Anfosso From the Institut national de la santé et de la recherche médicale (INSERM) UMR608 Physiopathologie de l'Endothélium, and INSERM ERM206 Technologies Avancées pour le Génome et la Clinique, Université Méditerranée, Marseille, France. Thrombin exerts pleiotropic effects on endothelial cells, including the release of microparticles (EMPs) that disseminate and exchange information with vascular cells. Nevertheless, the mechanisms leading to their generation are not elucidated. We performed microarray analysis to identify genes involved in EMP release by the endothelial cell line HMEC-1 in response to thrombin. We identified a group of genes linked to the cytoskeleton reorganization family. Among these, the Rho-kinase ROCK-II presented a high transcription rate. ROCK-I, another Rho-kinase isoform, was not modulated by thrombin. Pharmacologic inhibition of Rho-kinases or specific depletion of ROCK-II by short interfering (si) RNA inhibited thrombin-induced EMP release. In contrast, ROCK-I mRNA silencing did not modify EMP generation by thrombin. Exposure of HMEC-1 to thrombin in presence of the caspase-2 selective inhibitor Z-VDVAD-FMK prevented ROCK-II cleavage and inhibited the thrombin-induced EMP release. These events were observed in absence of cell death. Our data clearly identified ROCK-II as a target of thrombin in EMP generation. They indicated that the 2 Rho-kinases did not share identical functions. The involvement of caspase-2 in ROCK-II activation independently of cell death points out a novel signaling pathway that emphasizes the proteolytic activity of caspase in EMP generation in response to cell activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. I. Borissoff, H. M.H. Spronk, S. Heeneman, and H. ten Cate Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc Res, June 1, 2009; 82(3): 392 - 403. [Abstract] [Full Text] [PDF] N. Mackman On the Trail of Microparticles Circ. Res., April 24, 2009; 104(8): 925 - 927. [Full Text] [PDF] S. Simoncini, M.-S. Njock, S. Robert, L. Camoin-Jau, J. Sampol, J.-R. Harle, C. Nguyen, F. Dignat-George, and F. Anfosso TRAIL/Apo2L Mediates the Release of Procoagulant Endothelial Microparticles Induced by Thrombin In Vitro: A Potential Mechanism Linking Inflammation and Coagulation Circ. Res., April 24, 2009; 104(8): 943 - 951. [Abstract] [Full Text] [PDF] G.P. van Nieuw Amerongen, C.M.L. Beckers, I.D. Achekar, S. Zeeman, R.J.P. Musters, and V.W.M. van Hinsbergh Involvement of Rho Kinase in Endothelial Barrier Maintenance Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2332 - 2339. [Abstract] [Full Text] [PDF]

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