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  1. Article ; Online: The role of platelets and von Willebrand factor in the procoagulant phenotype of inflammatory bowel disease.

    Schellenberg, Célia / Lagrange, Jérémy / Ahmed, Muhammad Usman / Arnone, Djésia / Campoli, Philippe / Louis, Huguette / Touly, Nina / Caron, Bénédicte / Plénat, François / Perrin, Julien / Lenting, Peter J / Regnault, Véronique / Lacolley, Patrick / Denis, Cécile V / Peyrin-Biroulet, Laurent

    Journal of Crohn's & colitis

    2023  

    Abstract: Objective: Although the risk for thrombosis is well documented for inflammatory bowel disease (IBD) patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Deciphering the actors responsible for the ... ...

    Abstract Objective: Although the risk for thrombosis is well documented for inflammatory bowel disease (IBD) patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Deciphering the actors responsible for the increased risk of thrombosis in IBD would help to improve management of this frequent complication.
    Design: We studied the interplay between platelets, coagulation, and von Willebrand factor (VWF) in 193 IBD patients and in experimental models (acute and chronic) of colitis in wild-type and VWF-deficient mice.
    Results: We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were able to detect the presence of active VWF (VWF in its platelet-binding conformation; 3.2±2.7µg/ml) in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were below 0.3µg/ml. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also manifested a significant worsening of colitis severity both in acute and chronic models.
    Conclusion: Platelets and VWF (including its active form) appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in hemostasis differs from its role in colic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.
    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2390120-2
    ISSN 1876-4479 ; 1873-9946
    ISSN (online) 1876-4479
    ISSN 1873-9946
    DOI 10.1093/ecco-jcc/jjad198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Impact of operational and marketing capabilities on firm performance

    Ahmed, Muhammad Usman / Kristal, Mehmet Murat / Pagell, Mark

    International journal of production economics Vol. 154 , p. 59-71

    evidence from economic growth and downturns

    2014  Volume 154, Page(s) 59–71

    Author's details Muhammad Usman Ahmed; Mehmet Murat Kristal; Mark Pagell
    Keywords Operational capability ; Marketing capability ; Functional importance ; Economic advantage ; Resilience
    Language English
    Size graph. Darst.
    Publisher Elsevier
    Publishing place Amsterdam [u.a.]
    Document type Article
    ZDB-ID 1092526-0 ; 2020829-7
    ISSN 0925-5273
    ISSN 0925-5273
    Database ECONomics Information System

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  3. Article: Complexity and the triple bottom line

    Wiengarten, Frank / Ahmed, Muhammad Usman / Fynes, Brian / Longoni, Annachiara / Pagell, Mark

    International journal of operations & production management : IJOPM ; the official journal of the European Operations Management Association, EUROMA Vol. 37, No. 9 , p. 1142-1163

    an information-processing perspective

    2017  Volume 37, Issue 9, Page(s) 1142–1163

    Author's details Frank Wiengarten, Muhammad Usman Ahmed, Annachiara Longoni and Mark Pagell and Brian Fynes
    Keywords Complexity ; Sustainability ; Triple bottom line ; Information-processing theory
    Language English
    Publisher Emerald
    Publishing place Bingley
    Document type Article
    ZDB-ID 762449-9 ; 2032083-8
    ISSN 0144-3577
    ISSN 0144-3577
    Database ECONomics Information System

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  4. Article ; Online: Respective roles of Glycoprotein VI and FcγRIIA in the regulation of αIIbβ3-mediated platelet activation to fibrinogen, thrombus buildup, and stability.

    Ahmed, Muhammad Usman / Receveur, Nicolas / Janus-Bell, Emily / Mouriaux, Clarisse / Gachet, Christian / Jandrot-Perrus, Martine / Hechler, Béatrice / Gardiner, Elizabeth E / Mangin, Pierre H

    Research and practice in thrombosis and haemostasis

    2021  Volume 5, Issue 5, Page(s) e12551

    Abstract: Background: The interplay between platelets and fibrinogen is the cornerstone of thrombus formation. Integrin αIIbβ3 is the main platelet adhesion receptor for fibrinogen and mediates an outside-in signal upon ligand binding that reinforces platelet ... ...

    Abstract Background: The interplay between platelets and fibrinogen is the cornerstone of thrombus formation. Integrin αIIbβ3 is the main platelet adhesion receptor for fibrinogen and mediates an outside-in signal upon ligand binding that reinforces platelet activation. In addition, FcγRIIA and glycoprotein VI (GPVI) contribute to platelet activation on fibrinogen, thereby participating in thrombus growth and stability. To date, the relative importance of these two immunoreceptor tyrosine-based activation motif-bearing receptors in these processes remains unknown.
    Objective: The aim of this study was to evaluate the relative contributions of FcγRIIA and GPVI to platelet activation on fibrinogen and subsequent thrombus growth and stability.
    Methods: We evaluated human and mouse platelet adhesion to fibrinogen in static assays and a flow-based approach to evaluate the contribution of FcγRIIA and GPVI to thrombus growth and stability.
    Results: We first confirmed that integrin αIIbβ3 is the key receptor supporting platelet adhesion and spreading on fibrinogen. Using human platelets treated with pharmacological blocking agents and transgenic mouse platelets expressing human receptors, data indicate that GPVI, but not FcγRIIA, plays a prominent role in platelet activation on fibrinogen. Moreover, using a flow-based assay, we observed that blockade of GPVI with 1G5, but not FcγRIIA with IV.3, prevents thrombus growth. Finally, we observed that 1G5, but not IV.3, promotes the disaggregation of thrombi formed on collagen in vitro.
    Conclusion: This study provides evidence that GPVI, but not FcγRIIA, induces platelet activation and spreading on fibrinogen, and promotes thrombus buildup and stability.
    Language English
    Publishing date 2021-07-02
    Publishing country United States
    Document type Journal Article
    ISSN 2475-0379
    ISSN (online) 2475-0379
    DOI 10.1002/rth2.12551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Differential Role of Glycoprotein VI in Mouse and Human Thrombus Progression and Stability.

    Janus-Bell, Emily / Ahmed, Muhammad Usman / Receveur, Nicolas / Mouriaux, Clarisse / Nieswandt, Bernhard / Gardiner, Elizabeth E / Gachet, Christian / Jandrot-Perrus, Martine / Mangin, Pierre H

    Thrombosis and haemostasis

    2020  Volume 121, Issue 4, Page(s) 543–546

    MeSH term(s) Animals ; Blood Platelets/metabolism ; Blood Platelets/pathology ; Disease Progression ; Gene Deletion ; Humans ; Mice ; Platelet Aggregation ; Platelet Membrane Glycoproteins/genetics ; Platelet Membrane Glycoproteins/metabolism ; Thrombosis/genetics ; Thrombosis/metabolism ; Thrombosis/pathology
    Chemical Substances Platelet Membrane Glycoproteins ; platelet membrane glycoprotein VI
    Language English
    Publishing date 2020-10-29
    Publishing country Germany
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1055/s-0040-1718737
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Pharmacological Blockade of Glycoprotein VI Promotes Thrombus Disaggregation in the Absence of Thrombin.

    Ahmed, Muhammad Usman / Kaneva, Valeria / Loyau, Stéphane / Nechipurenko, Dmitry / Receveur, Nicolas / Le Bris, Marion / Janus-Bell, Emily / Didelot, Mélusine / Rauch, Antoine / Susen, Sophie / Chakfé, Nabil / Lanza, François / Gardiner, Elizabeth E / Andrews, Robert K / Panteleev, Mikhail / Gachet, Christian / Jandrot-Perrus, Martine / Mangin, Pierre H

    Arteriosclerosis, thrombosis, and vascular biology

    2020  Volume 40, Issue 9, Page(s) 2127–2142

    Abstract: Objective: Atherothrombosis occurs upon rupture of an atherosclerotic plaque and leads to the formation of a mural thrombus. Computational fluid dynamics and numerical models indicated that the mechanical stress applied to a thrombus increases ... ...

    Abstract Objective: Atherothrombosis occurs upon rupture of an atherosclerotic plaque and leads to the formation of a mural thrombus. Computational fluid dynamics and numerical models indicated that the mechanical stress applied to a thrombus increases dramatically as a thrombus grows, and that strong inter-platelet interactions are essential to maintain its stability. We investigated whether GPVI (glycoprotein VI)-mediated platelet activation helps to maintain thrombus stability by using real-time video-microscopy. Approach and Results: We showed that GPVI blockade with 2 distinct Fab fragments promoted efficient disaggregation of human thrombi preformed on collagen or on human atherosclerotic plaque material in the absence of thrombin. ACT017-induced disaggregation was achieved under arterial blood flow conditions, and its effect increased with wall shear rate. GPVI regulated platelet activation within a growing thrombus as evidenced by the loss in thrombus contraction when GPVI was blocked, and the absence of the disaggregating effect of an anti-GPVI agent when the thrombi were fully activated with soluble agonists. The GPVI-dependent thrombus stabilizing effect was further supported by the fact that inhibition of any of the 4 key immunoreceptor tyrosine-based motif signalling molecules, src-kinases, Syk, PI3Kβ, or phospholipase C, resulted in kinetics of thrombus disaggregation similar to ACT017. The absence of ACT017-induced disaggregation of thrombi from 2 afibrinogenemic patients suggests that the role of GPVI requires interaction with fibrinogen. Finally, platelet disaggregation of fibrin-rich thrombi was also promoted by ACT017 in combination with r-tPA (recombinant tissue plasminogen activator).
    Conclusions: This work identifies an unrecognized role for GPVI in maintaining thrombus stability and suggests that targeting GPVI could dissolve platelet aggregates with a poor fibrin content.
    MeSH term(s) Afibrinogenemia/blood ; Afibrinogenemia/diagnosis ; Afibrinogenemia/genetics ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Computer Simulation ; Fibrinogen/genetics ; Fibrinogen/metabolism ; Fibrinolytic Agents/pharmacology ; Humans ; Immunoglobulin Fab Fragments/pharmacology ; Kinetics ; Microscopy, Video ; Models, Biological ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Membrane Glycoproteins/antagonists & inhibitors ; Platelet Membrane Glycoproteins/metabolism ; Signal Transduction ; Stress, Mechanical ; Thrombin/metabolism ; Thrombosis/blood ; Thrombosis/diagnosis ; Thrombosis/drug therapy ; Thrombosis/genetics
    Chemical Substances Fibrinolytic Agents ; Immunoglobulin Fab Fragments ; Platelet Aggregation Inhibitors ; Platelet Membrane Glycoproteins ; platelet membrane glycoprotein VI ; Fibrinogen (9001-32-5) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2020-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.120.314301
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Differential Role of Glycoprotein VI in Mouse and Human Thrombus Progression and Stability

    Janus-Bell, Emily / Ahmed, Muhammad Usman / Receveur, Nicolas / Mouriaux, Clarisse / Nieswandt, Bernhard / Gardiner, Elizabeth E. / Gachet, Christian / Jandrot-Perrus, Martine / Mangin, Pierre H.

    Thrombosis and Haemostasis

    2020  Volume 121, Issue 04, Page(s) 543–546

    Language English
    Publishing date 2020-10-29
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1055/s-0040-1718737
    Database Thieme publisher's database

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