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Clumping factor A, von Willebrand factor-binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall Institute of Tropical Medicine KU Leuven

Jean Claes, Laurens Liesenborghs, ME Peetermans, Tiago Rafael Veloso, Dominique Missiakas, Olaf Schneewind, Silvia Mancini, Jose M Entenza, Marc F Hoylaerts, Ruth Heying, et al.

UNLABELLED: Essentials Staphylococcus aureus (S. aureus) binds to endothelium via von Willebrand factor (VWF). Secreted VWF-binding protein (vWbp) mediates S. aureus adhesion to VWF under shear stress. vWbp interacts with VWF and the Sortase A-dependent surface protein Clumping factor A (ClfA). VWF-vWbp-ClfA anchor S. aureus to vascular endothelium under shear stress.

SUMMARY: Objective When establishing endovascular infections, ...

von Willebrand factor in experimental malaria-associated acute respiratory distress syndrome Institute of Tropical Medicine KU Leuven

Sirima Kraisin, Sebastien Verhenne, Thy, Kimberly Martinod, Claudia Tersteeg, Nele Vandeputte, Hans Deckmyn, Karen Vanhoorelbeke, Philippe E. Van den Steen, Simon F De Meyer, et al.

Background: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a lethal complication of severe malaria, characterized by marked pulmonary inflammation. Patient studies have suggested a link between von Willebrand factor (VWF) and malaria severity.

Objectives: To investigate the role of VWF in the pathogenesis of experimental MA-ARDS.

Methods: Plasmodium berghei NK65-E (PbNK65) parasites were injected in Vwf+/+ ...

Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor-binding protein Institute of Tropical Medicine KU Leuven

Jorien Claes, Thomas Vanassche, Marijke Peetermans, Laurens Liesenborghs, Christophe Vandenbriele, Karen Vanhoorelbeke, Dominique Missiakas, Olaf Schneewind, Marc F Hoylaerts, Ruth Heying, et al.

Adhesion of Staphylococcus aureus to blood vessels under shear stress requires von Willebrand factor (VWF). Several bacterial factors have been proposed to interact with VWF, including VWF-binding protein (vWbp), a secreted coagulase that activates the host's prothrombin to generate fibrin. We measured the adhesion of S aureus Newman and a vWbp-deficient mutant (vwb) to VWF, collagen, and activated endothelial cells in a microparallel flow ...

Shear-resistant binding to von Willebrand factor allows Staphylococcus lugdunensis to adhere to the cardiac valves and initiate endocarditis Institute of Tropical Medicine KU Leuven

Laurens Liesenborghs, Marijke Peetermans, Jorien Claes, Tiago Rafael Veloso, Christophe Vandenbriele, Maarten Criel, Marleen Lox, Willy E Peetermans, Simon Heilbronner, Philip G de Groot, et al.

BACKGROUND: Staphylococcus lugdunensis is an emerging cause of endocarditis. To cause endovascular infections, S. lugdunensis requires mechanisms to overcome shear stress. We investigated whether platelets and von Willebrand factor (VWF) mediate bacterial adhesion to the vessel wall and the cardiac valves under flow.

METHODS: S. lugdunensis binding to VWF, collagen, and endothelial cells was studied in a parallel flow chamber in the ...

Sleeping Beauty transposon-mediated gene therapy for von Willebrand disease and the role of von Willebrand factor in abdominal aortic aneurysm KU Leuven

Irina Portier
Von Willebrand disease (VWD) is the most common inherited bleeding disorder in man. It is caused by genetic defects in von Willebrand factor (VWF), a blood protein that is crucial for normal hemostasis. VWD type 3 is the most severe form, characterized by a complete absence of VWF protein. Direct administration of VWF/FVIII containing blood products is currently the only treatment option for VWD type 3. This treatment has however only a ...

Factor VIII-von Willebrand Factor Binding Defects in Autosomal Recessive von Willebrand Disease Type Normandy and in Mild Hemophilia A New Insights into Factor VIII-von Willebrand Factor Interactions KU Leuven

Marc Jacquemin
This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but causes an accelerated clearance of FVIII. Missense mutations in the FVIII ...

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis Institute of Tropical Medicine KU Leuven

Marijke Peetermans, Severien Meyers, Laurens Liesenborghs, Karen Vanhoorelbeke, Simon F De Meyer, Christophe Vandenbriele, Marleen Lox, Marc F Hoylaerts, Kimberly Martinod, Marc Jacquemin, et al.

BACKGROUND: Previous clinical evidence correlates levels of von Willebrand factor (VWF) and its cleaving protease ADAMTS13 with outcome in septic patients. No previous studies addressed if VWF and ADAMTS13 affected the outcome of Staphylococcus aureus sepsis.

OBJECTIVES: We studied the role of VWF and ADAMTS13 in S. aureus sepsis both in patients and in mice.

METHODS: VWF levels and ADAMTS13 activity levels were measured in ...

Keeping von Willebrand Factor under Control: Alternatives for ADAMTS13 KU Leuven

Claudia Tersteeg, Rob Fijnheer, Gerard Pasterkamp, Philip G de Groot, Karen Vanhoorelbeke, Steven de Maat, Coen Maas
Von Willebrand factor (VWF) is one of the most important proteins of the hemostatic system. Its multimeric state is essential for its natural function to guide platelets to sites of injury. ADAMTS13 is the key protease that regulates the multimeric state of VWF. Without ADAMTS13, VWF multimers can grow to pathologically large sizes. This is a risk factor for the life-threatening condition thrombotic thrombocytopenic purpura (TTP). In this ...

Keeping von Willebrand Factor under Control: Alternatives for ADAMTS13 KU Leuven

Claudia Tersteeg, Karen Vanhoorelbeke
Von Willebrand factor (VWF) is one of the most important proteins of the hemostatic system. Its multimeric state is essential for its natural function to guide platelets to sites of injury. ADAMTS13 is the key protease that regulates the multimeric state of VWF. Without ADAMTS13, VWF multimers can grow to pathologically large sizes. This is a risk factor for the life-threatening condition thrombotic thrombocytopenic purpura (TTP). In this ...

Analysis of von Willebrand Disease in the South Moravian Population (Czech Republic): Results from the BRNO-VWD Study University of Antwerp

Inge Vangenechten, Petr Smejkal, Ondrej Zapletal, Jan Jacques Michiels, Zwi Berneman, Jiri Zavrelova, Jan Blatny, Miroslav Penka, Alain Gadisseur
Background von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von Willebrand factor (VWF). The heterogeneity of laboratory phenotyping makes diagnosing difficult. Objective A cross-sectional, family-based VWD study in a collaboration between University Hospital Brno (Czech Republic) and Antwerp University Hospital (Belgium) to improve the understanding of ...