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Citations to this article

P2X7 receptor signaling contributes to tissue factor–dependent thrombosis in mice
Christian Furlan-Freguia, … , Zaverio M. Ruggeri, Wolfram Ruf
Christian Furlan-Freguia, … , Zaverio M. Ruggeri, Wolfram Ruf
Published June 13, 2011
Citation Information: J Clin Invest. 2011;121(7):2932-2944. https://doi.org/10.1172/JCI46129.
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Research Article Hematology Article has an altmetric score of 4

P2X7 receptor signaling contributes to tissue factor–dependent thrombosis in mice

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Abstract

Thrombosis is initiated by tissue factor (TF), a coagulation cofactor/receptor expressed in the vessel wall, on myeloid cells, and on microparticles (MPs) with variable procoagulant activity. However, the molecular pathways that generate prothrombotic TF in vivo are poorly defined. The oxidoreductase protein disulfide isomerase (PDI) is thought to be involved in the activation of TF. Here, we found that in mouse myeloid cells, ATP-triggered signaling through purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7 receptor; encoded by P2rx7) induced activation (decryption) of TF procoagulant activity and promoted release of TF+ MPs from macrophages and SMCs. The generation of prothrombotic MPs required P2X7 receptor–dependent production of ROS leading to increased availability of solvent-accessible extracellular thiols. An antibody to PDI with antithrombotic activity in vivo attenuated the release of procoagulant MPs. In addition, P2rx7–/– mice were protected from TF-dependent FeCl3-induced carotid artery thrombosis. BM chimeras revealed that P2X7 receptor prothrombotic function was present in both hematopoietic and vessel wall compartments. In contrast, an alternative anti-PDI antibody showed activities consistent with cellular activation typically induced by P2X7 receptor signaling. This anti-PDI antibody restored TF-dependent thrombosis in P2rx7–/– mice. These data suggest that PDI regulates a critical P2X7 receptor–dependent signaling pathway that generates prothrombotic TF, defining a link between inflammation and thrombosis with potential implications for antithrombotic therapy.

Authors

Christian Furlan-Freguia, Patrizia Marchese, András Gruber, Zaverio M. Ruggeri, Wolfram Ruf

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 5 2 5 9 5 7 4 10 8 2 8 8 9 8 90
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2012 (8)

Title and authors Publication Year
Protein disulfide isomerase inhibitors constitute a new class of antithrombotic agents.
Reema Jasuja, Freda H. Passam, Daniel R. Kennedy, Sarah H. Kim, Lotte van Hessem, Lin Lin, Sheryl R. Bowley, Sucharit S. Joshi, James R. Dilks, Bruce Furie, Barbara C. Furie, Robert Flaumenhaft
Journal of Clinical Investigation 2012
Ectonucleotide Triphosphate Diphosphohydrolase-1 (CD39) Mediates Resistance to Occlusive Arterial Thrombus Formation after Vascular Injury in Mice
ZM Huttinger, MW Milks, MS Nickoli, WL Aurand, LC Long, DG Wheeler, KM Dwyer, AJ d'Apice, SC Robson, PJ Cowan, RJ Gumina
The American Journal of Pathology 2012
Regulation of tissue factor coagulant activity on cell surfaces
LV Rao, UR Pendurthi
Journal of Thrombosis and Haemostasis 2012
Tissue Factor encryption and decryption: Facts and controversies
LV Rao, H Kothari, UR Pendurthi
Thrombosis Research 2012
Role of thiol pathways in TF procoagulant regulation
W Ruf
Thrombosis Research 2012
Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling
C Reinhardt, M Bergentall, TU Greiner, F Schaffner, G Östergren-Lundén, LC Petersen, W Ruf, F Bäckhed
Nature 2012
A Common Missense Variant in the ATP Receptor P2X7 Is Associated with Reduced Risk of Cardiovascular Events
O Gidlöf, JG Smith, O Melander, H Lövkvist, B Hedblad, G Engström, P Nilsson, J Carlson, G Berglund, S Olsson, K Jood, C Jern, B Norrving, A Lindgren, D Erlinge
PloS one 2012
P2X7 regulation of macrophage tissue factor activity and microparticle generation
R Lee, JC Williams, N Mackman
Journal of Thrombosis and Haemostasis 2012

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