Interaction between major pathways for platelet activation in mouse models of arterial thrombosis

Objective

Platelets play a central role in arterial thrombosis, causing life-threatening and disabling diseases like myocardial infarction and ischemic stroke. Despite antiplatelet therapies have been proven efficacious for primary and secondary prevention of cardio- and cerebrovascular diseases, arterial thrombosis remains a major healthy problem. A better understanding of the multiple mechanisms by which platelets can be activated is the basis for the rationale development of new antithrombotic drugs. The “outgoing” host institution involved in this project has previously demonstrated that protease-activated receptor (PAR) signaling in platelets is necessary for platelet activation by thrombin and important for hemostasis and thrombosis in mouse models. These results have greatly contributed to the development of a PAR1 antagonist, that has been recently used as antithrombotic drug in a phase II trial . The objectives of this proposal are to better define the role of thrombin signaling in vivo and to explore how the thrombin-PARs pathway relates to other effectors of hemostasis and thrombosis. This study will make use of mouse models of hemostasis and thrombosis. In the partner institution the generation of knockout mice for multiple platelet receptors (glycoprotein VI, FcγR, P2Y12 ) and other relevant molecules for hemostasis and thrombosis (vonWillebrand factor, FIX, FXI, fibrinogen) is ongoing. On those mice the following endpoints will be evaluated 1) hemostasis (bleeding time, neonatal hemorrhage, placentation, maternal hemorrhage, anemia) 2) thrombosis (by using a ferric chloride injury to induce carotid or mesenteric thrombosis). This project will allow the researcher to gain knowledge and experience on the in vivo models of hemostasis and thrombosis. This will be relevant for the fellowship program since the in vivo models will be set up during the return phase in the host institution.

Fields of science

• medical and health sciencesclinical medicinehematology
• medical and health sciencesbasic medicineneurologystroke
• medical and health sciencesclinical medicineangiologyvascular diseasescerebrovascular diseases

Keywords

• Cardiology
• Health sciences
• Medical sciences

Programme(s)

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

• PEOPLE-2007-4-1.IOF - Marie Curie Action: "International Outgoing Fellowships for Career Development"

Call for proposal

FP7-PEOPLE-2007-4-1-IOF
See other projects for this call

Funding Scheme

Coordinator