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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.

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

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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