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Molecular mechanisms of platelet-vessel wall interactions: an assessment of experimental thrombosis based on real time technologies

Objective

Thrombotic occlusion of atherosclerotic coron arteries is the common cause of acute myocardial infarction, and platelet-dependent thrombotic diseases are the first cause of death in the Westem Society. The general objective of this joint research project is to establish a highly competitive open- wall research and training infrastructure in thrombosis, based on the complementary expertise of 7 leading European laboratories, who have combined their efforts in a multidisciplinary approach to
(a) investigate the molecular mechanisms underlying blood-platelet interactions with the vasculature,
(b ) develop cell-type and receptor specific antagonists that will prevent uncontrolled platelet adhesion events leading to cardiovascular diseases, and
(c) use state-of -the-art real time technologies to assess the efficiency of these antagonists in flowing blood conditions in vitro and in vivo.
At the scientific level, our objectives are
(1) to define the three-dimensional structural requirements necessary for the interaction of major prothrombogenic matrix proteins such as collagen and vWF with their respective receptors (integrins alpha2Beta1 and alphaIIBeta3, GPIb), using recombinant proteins for cocrystallisation experiments and atomic force microscopy analysis;
(2) to design and synthesize small triple helical collagen-derived peptides as collagen mimetics;
(3) to identify new receptor antagonists by screening parasite extracts and parasite-derived cDNA expression libraries, peptide and antibody display libraries;
(4) to use platelet proteomics and MALDI- TOF technology to identify new intracellular integrin receptor ligands as potential targets for anti-thrombotic drug development, and
(5) to generate new prothrombotic mice models through transgenic knock-in technology. A major objective of this network is to offer young predoctoral and postdoctoral EU-scientists high quality training in a broad spectrum of state-of-the-art technologies applied to cardio

Funding Scheme

NET - Research network contracts

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue Du Général Leclerc 84
94276 Le Kremlim Bicetre
France

Participants (6)

CENTRE DE RECHERCHE PUBLIC DE LA SANTE
Luxembourg
Address
162 A,avenue De La Faiencerie 162 A, Centre Universitair
1511 Luxembourg
KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium
Address
53,E. Sabbelaan 53 Universitaire Campus
8500 Kortrijk
ROYAL COLLEGE OF SURGEONS IN IRELAND
Ireland
Address
Saint Stephen's Green 123
Dublin
UNIVERSITY MEDICAL CENTRE UTRECHT
Netherlands
Address
Heidelberglaan 100
3584CX Utrecht
UNIVERSITY OF DEBRECEN
Hungary
Address
Nagyerdei Krt. 98
4012 Debrecen
UNIVERSITY OF NOTTINGHAM
United Kingdom
Address
University Park
NG7 2RD Nottingham