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VWF and NETs

Investigating the interplay between VWF, platelets, and neutrophil extracellular traps in pathologies involving thrombosis of the microvasculature

Total Cost €

0

EC-Contrib. €

0

Partnership

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 VWF and NETs project word cloud

Explore the words cloud of the VWF and NETs project. It provides you a very rough idea of what is the project "VWF and NETs" about.

inflammatory    von    mediated    diseases    traps    effect    netosis    sirs    summary    induction    proteases    disease    innovative    chromatin    platelet    concentrated    body    selectin    cell    red    dna    stimulate    neutrophils    mutants    clinical    malaria    cycle    flow    turn    proteins    mediator    understand    models    thrombo    form    activation    contents    options    myeloperoxidase    inhibition    mouse    neutrophil    involvement    containing    relevance    vicious    contributes    treatment    drive    function    leukocytes    blood    combined    discovery    cells    pathologies    kinetics    severe    extracellular    net    recruits    critical    strategies    live    therapeutic    vwf    strands    microvascular    activated    unravel    settings    aggregates    thrombocytopenic    antimicrobial    sudden    interactions    space    mortality    platelets    progression    purpura    thrombosis    thrombotic    microbicidal    physiological    endothelial    cytometry    imaging    inflammation    palade    multiorgan    pathology    ttp    elucidate    first    syndrome    limited    inhibiting    willebrand    bind    weibel    serine    fibers    histones    nets    release   

Project "VWF and NETs" data sheet

The following table provides information about the project.

Coordinator
KATHOLIEKE UNIVERSITEIT LEUVEN 

Organization address
address: OUDE MARKT 13
city: LEUVEN
postcode: 3000
website: www.kuleuven.be

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Belgium [BE]
 Project website https://www.kuleuven.be/english/research/EU/p/horizon2020/es/msca/if-projects/vwfandnets
 Total cost 160˙800 €
 EC max contribution 160˙800 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-10-03   to  2019-10-02

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KATHOLIEKE UNIVERSITEIT LEUVEN BE (LEUVEN) coordinator 160˙800.00

Map

 Project objective

Thrombosis is a complex process involving activation of endothelial cells, and their release of Weibel-Palade body contents such as von Willebrand factor (VWF) and P-selectin. This in turn recruits platelets which form aggregates, and leukocytes such as neutrophils. The recent discovery of neutrophil extracellular traps (NETs) described a novel antimicrobial function of neutrophils. NETs are extracellular chromatin strands containing microbicidal proteins. The release of histones, serine proteases, and myeloperoxidase concentrated on DNA fibers into the extracellular space can contribute to many pathologies. NETs can bind platelets and red blood cells and therefore also contribute to thrombosis. Activated platelets can in turn stimulate neutrophils to make NETs, creating a vicious thrombo-inflammatory cycle.

Our first objective is to study VWF involvement in the induction of NETosis. We will elucidate the role of VWF as an important mediator of NET formation using VWF mutants. Innovative live-cell imaging and flow cytometry will be used to unravel the kinetics of VWF/platelet-mediated NET formation. Our second objective is to assess the physiological relevance of (inhibiting) platelet/VWF involvement in NETs-related pathology. We will investigate the role of VWF/NET interactions in three critical clinical settings where microvascular thrombosis contributes to multiorgan failure and/or mortality: sudden inflammatory response syndrome (SIRS), thrombotic thrombocytopenic purpura (TTP), and severe malaria. Mouse models of disease will be used and combined with several strategies for inhibition of VWF/platelet/NETs interactions to assess their effect on disease progression.

In summary, with this research project we aim to better understand how platelets and VWF can drive NET formation in thrombo-inflammation, as this may also lead to more targeted therapeutic approaches in diseases which currently have limited treatment options.

 Publications

year authors and title journal last update
List of publications.
2019 Nicoletta Sorvillo, Deya Cherpokova, Kimberly Martinod, Denisa D. Wagner
Extracellular DNA NET-Works With Dire Consequences for Health
published pages: 470-488, ISSN: 0009-7330, DOI: 10.1161/circresaha.119.314581
Circulation Research 125/4 2020-02-20
2019 Sirima Kraisin, Sebastien Verhenne, Thao‐Thy Pham, Kimberly Martinod, Claudia Tersteeg, Nele Vandeputte, Hans Deckmyn, Karen Vanhoorelbeke, Philippe E. Van den Steen, Simon F. De Meyer
von Willebrand factor in experimental malaria‐associated acute respiratory distress syndrome
published pages: 1372-1383, ISSN: 1538-7933, DOI: 10.1111/jth.14485
Journal of Thrombosis and Haemostasis 17/8 2020-02-20
2018 K. Martinod, T. A. Fuchs
What a drag: necrotic platelets induce remote neutrophil thrombi following ischemic gut injury
published pages: 819-821, ISSN: 1538-7933, DOI: 10.1111/jth.13989
Journal of Thrombosis and Haemostasis 16/5 2020-02-20
2018 Martinod K, Fuchs TA.
What a drag: necrotic platelets induce remote neutrophil thrombi following ischemic gut injury
published pages: , ISSN: 1538-7933, DOI: 10.1111/jth.13989
J Thromb Haemost 2020-02-20
2019 Elodie Laridan, Kimberly Martinod, Simon De Meyer
Neutrophil Extracellular Traps in Arterial and Venous Thrombosis
published pages: 086-093, ISSN: 0094-6176, DOI: 10.1055/s-0038-1677040
Seminars in Thrombosis and Hemostasis 45/01 2020-02-20

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