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  1. Article ; Online: Stabilin-2 deficiency increases thrombotic burden and alters the composition of venous thrombi in a mouse model.

    Michels, Alison / Swystun, Laura L / Dwyer, Courtney N / Rawley, Orla / Nesbitt, Kate / Notley, Colleen / Lillicrap, David

    Journal of thrombosis and haemostasis : JTH

    2021  Volume 19, Issue 10, Page(s) 2440–2453

    Abstract: Background: Stabilin-2 is an endocytic scavenger receptor that mediates the clearance of glycosaminoglycans, phosphatidylserine-expressing cells, and the von Willebrand factor-factor VIII (FVIII) complex. In a genome-wide screening study, pathogenic ... ...

    Abstract Background: Stabilin-2 is an endocytic scavenger receptor that mediates the clearance of glycosaminoglycans, phosphatidylserine-expressing cells, and the von Willebrand factor-factor VIII (FVIII) complex. In a genome-wide screening study, pathogenic loss-of-function variants in the human STAB2 gene associated with an increased incidence of unprovoked venous thromboembolism (VTE). However, the specific mechanism(s) by which stabilin-2 deficiency influences the pathogenesis of VTE is unknown.
    Objectives: The aim of this study was to assess the influence of stabilin-2 on deep vein thrombosis (DVT) and to characterize the underlying prothrombotic phenotype of stabilin-2 deficiency in a mouse model.
    Methods: DVT was induced using the inferior vena cava (IVC) stenosis model in two independent cohorts (littermates and non-littermates) of wild-type (Stab2
    Results: Incidence of thrombus formation was not altered between Stab2
    Conclusions: These data suggest that stabilin-2 deficiency associates with a prothrombotic phenotype involving elevated levels of neutrophil extracellular trap-releasing leukocytes coupled with endogenous procoagulant activity, resulting in larger and qualitatively distinct venous thrombi.
    MeSH term(s) Animals ; Cell Adhesion Molecules, Neuronal ; Disease Models, Animal ; Extracellular Traps ; Mice ; Mice, Knockout ; Thrombosis ; Veins ; von Willebrand Factor
    Chemical Substances Cell Adhesion Molecules, Neuronal ; Stab2 protein, mouse ; von Willebrand Factor
    Language English
    Publishing date 2021-07-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1111/jth.15429
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5805: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 295: Show issues

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  2. Article ; Online: The mechanistic and structural role of von Willebrand factor in endotoxemia-enhanced deep vein thrombosis in mice.

    Choi, Seon Jae / Dwyer, Courtney N / Rapkin, Lindsy / Cormier, Matthew / Hindmarch, Charles C T / Nesbitt, Kate / Michels, Alison / Hopman, Wilma / Swystun, Laura L / Lillicrap, David

    Journal of thrombosis and haemostasis : JTH

    2022  Volume 21, Issue 3, Page(s) 586–598

    Abstract: Background: Although the concept of immunothrombosis has established a link between inflammation and thrombosis, the role of inflammation in the pathogenesis of deep vein thrombosis remains to be fully elucidated. Further, although various constituents ... ...

    Abstract Background: Although the concept of immunothrombosis has established a link between inflammation and thrombosis, the role of inflammation in the pathogenesis of deep vein thrombosis remains to be fully elucidated. Further, although various constituents of venous thrombi have been identified, their localizations and cellular and molecular interactions are yet to be combined in a single, multiplexed analysis.
    Objectives: The objective of this study was to investigate the role of the von Willebrand factor (VWF) in inflammation-associated venous thrombosis. We also performed a proof-of-concept study of imaging mass cytometry to quantitatively and simultaneously analyze the localizations and interactions of 10 venous thrombus constituents.
    Methods: We combined the murine inferior vena cava stenosis model of deep vein thrombosis with the lipopolysaccharide model of endotoxemia. We also performed a proof-of-concept study of imaging mass cytometry to assess the feasibility of this approach in analyzing the structural composition of thrombi.
    Results: We found that lipopolysaccharide-treated mice had significantly higher incidences of venous thrombosis, an effect that was mitigated when VWF was inhibited using inhibitory αVWF antibodies. Our detailed structural analysis also showed that most thrombus components are localized in the white thrombus regardless of endotoxemia. Moreover, although endotoxemia modulated the relative representation and interactions of VWF with other thrombus constituents, the scaffolding network, comprised VWF, fibrin, and neutrophil extracellular traps, remained largely unaffected.
    Conclusions: We observe a key role for VWF in the pathogenesis of inflammation-associated venous thrombosis while providing a more comprehensive insight into the molecular interactions that constitute the architecture of venous thrombi.
    MeSH term(s) Mice ; Animals ; von Willebrand Factor ; Endotoxemia ; Lipopolysaccharides ; Venous Thrombosis/etiology ; Thrombosis/complications
    Chemical Substances von Willebrand Factor ; Lipopolysaccharides
    Language English
    Publishing date 2022-12-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2022.11.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5805: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 295: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: von Willebrand Factor Is a Critical Mediator of Deep Vein Thrombosis in a Mouse Model of Diet-Induced Obesity.

    Michels, Alison / Dwyer, Courtney N / Mewburn, Jeffrey / Nesbitt, Kate / Kawecki, Charlotte / Lenting, Peter / Swystun, Laura L / Lillicrap, David

    Arteriosclerosis, thrombosis, and vascular biology

    2020  Volume 40, Issue 12, Page(s) 2860–2874

    Abstract: Objective: Obesity is characterized by chronic low-grade inflammation and consequentially a hypercoagulable state, associating with an increased incidence of venous thromboembolism. Increased VWF (von Willebrand factor) plasma concentration and ... ...

    Abstract Objective: Obesity is characterized by chronic low-grade inflammation and consequentially a hypercoagulable state, associating with an increased incidence of venous thromboembolism. Increased VWF (von Willebrand factor) plasma concentration and procoagulant function are independent risk factors for venous thromboembolism and are elevated in obese patients. Here, we explore the pathobiological role of VWF in obesity-associated venous thrombosis using murine models. Approach and Results: We first showed that diet-induced obese mice have increased VWF plasma levels and FVIII (factor VIII) activity compared with littermate controls. Elevated VWF levels appeared to be because of both increased synthesis and impaired clearance. Diet-induced obesity-associated venous thrombosis was assessed using the inferior vena cava-stenosis model of deep vein thrombosis. Diet-induced obese mice developed larger venous thrombi that were rich in VWF, erythrocytes, and leukocytes. Administering a polyclonal anti-VWF antibody or an anti-VWF A1 domain nanobody was protective against obesity-mediated thrombogenicity. Delayed administration (3 hours post-inferior vena cava stenosis) similarly reduced thrombus weight in diet-induced obese mice.
    Conclusions: This study demonstrates the critical role of VWF in the complex, thrombo-inflammatory state of obesity. It adds to the growing rationale for targeting VWF-specific interactions in thrombotic disease.
    MeSH term(s) ADAMTS13 Protein/genetics ; ADAMTS13 Protein/metabolism ; Animals ; Diet, High-Fat ; Disease Models, Animal ; Female ; Fibrinolytic Agents/pharmacology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/complications ; Obesity/metabolism ; Signal Transduction ; Single-Domain Antibodies/pharmacology ; Vena Cava, Inferior/drug effects ; Vena Cava, Inferior/metabolism ; Vena Cava, Inferior/pathology ; Venous Thrombosis/etiology ; Venous Thrombosis/metabolism ; Venous Thrombosis/pathology ; Venous Thrombosis/prevention & control ; von Willebrand Factor/antagonists & inhibitors ; von Willebrand Factor/genetics ; von Willebrand Factor/metabolism
    Chemical Substances Fibrinolytic Agents ; Single-Domain Antibodies ; von Willebrand Factor ; ADAMTS13 protein, mouse (EC 3.4.24.-) ; ADAMTS13 Protein (EC 3.4.24.87)
    Language English
    Publishing date 2020-09-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.120.314690
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1705: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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