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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4155-4164. Prepublished online as a Blood First Edition Paper on February 11, 2008; DOI 10.1182/blood-2007-10-120295. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-120295v1 111/8/4155    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 Chen, D. Articles by Dorling, A. Search for Related Content PubMed PubMed Citation Articles by Chen, D. Articles by Dorling, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Regenerative repair after endoluminal injury in mice with specific antagonism of protease activated receptors on CD34+ vascular progenitors Daxin Chen1, Joel M. Abrahams1, Leanne M. Smith1, John H. McVey2, Robert I. Lechler1, and Anthony Dorling1 1 Department of Immunology, Imperial College London, Hammersmith Hospital, London; and 2 Haemostasis and Thrombosis Unit, Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, United Kingdom Tissue factor (TF) and thrombin are involved in intimal hyperplasia (IH) and remodelling following vascular injury. Because many neointimal smooth muscle cells (VSMCs) derive from circulating vascular progenitors (VPs), we investigated how thrombin influences VP phenotype and function. Following wire-induced carotid artery injury in mice, the majority of circulating VPs expressed TF, were capable of initiating clotting in vitro, and had protease-activated receptors (PAR)–1, –2, and –4. Thrombin, through PAR-1, inhibited apoptosis and caused proliferation, resulting in the outgrowth of VP coexpressing markers of activated endothelial cells and VSMCs, even in the presence of growth factors. These mixed-phenotype VPs circulated as a minority population after injury and shared a similar phenotype with many neointimal cells. Labeled CD34+ cells, injected up to 2 weeks after injury, could be detected in the injured vessel wall, suggesting that continued recruitment may contribute to progressive IH. Finally, CD34+ cells incubated with thrombin prior to injection promoted florid neointimal lesions, whereas those incubated with PAR antagonists inhibited IH and promoted regenerative repair characterized by the development of a quiescent endothelium. We conclude that IH after vascular injury is due to the direct actions of thrombin on mobilized VPs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Martin, S. Weiss, P. Metharom, J. Schmeckpeper, B. Hynes, J. O'Sullivan, and N. Caplice Thrombin Stimulates Smooth Muscle Cell Differentiation From Peripheral Blood Mononuclear Cells via Protease-Activated Receptor-1, RhoA, and Myocardin Circ. Res., July 31, 2009; 105(3): 214 - 218. [Abstract] [Full Text] [PDF]

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