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Studies on platelet receptors in relation to haemostasis and thrombosis

English title Studies on platelet receptors in relation to haemostasis and thrombosis
Applicant Clemetson Kenneth J.
Number 107754
Funding scheme Project funding (Div. I-III)
Research institution Theodor Kocher Institut Universität Bern
Institution of higher education University of Berne - BE
Main discipline Biochemistry
Start/End 01.04.2005 - 31.05.2008
Approved amount 479'000.00
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Keywords (6)

platelets; thrombosis; haemostasis; receptors; serotonin; collagen

Lay Summary (English)

Lead
Lay summary
Cardiovascular diseases, including heart attacks and stroke, remain the major cause of death and disablement in Western countries and many developing countries are rapidly catching up. Haemostasis is the physiological process to prevent blood loss after injury and thrombosis its pathological equivalent. Both involve coagulation factors and blood platelets. Platelets are the smallest cellular element in the blood and a critical component of haemostasis. A low platelet count - thrombocytopenia - can lead to life threatening bleeding. On the other hand, over sensitive or activated platelets can lead to thrombosis. Thus, it is important to understand how platelets work and the roles of their individual components, in particular surface receptors, which have been and still are the targets of research to produce inhibitors to prevent and treat thrombosis.Our research is directed towards a better understanding of the structure and function of platelet receptors as well as their interactions with agonists, connective tissue, between platelets to form aggregates and with leukocytes in the process of inflammation. Platelet receptors also have roles in defense against pathogens such as bacteria and viruses, and in inate immunology, all of which are still poorly understood. Our studies focus on two major receptors, the collagen receptor GPVI and the von Willebrand factor receptor GPIb-V-IX. Both of these are involved in early adhesion events during platelet binding to injured vessel or inflamed endothelium. They are both down regulated following activation, by both proteolysis and removal from the platelet surface, in a tightly regulated way. Signalling pathways from these receptors have also been extensively investigated but there is a lot still to do and proteomic tools have opened new possibilities. Both of these receptors are seen worldwide by the pharmaceutical industry as important targets for new anti-thrombotic treatments and also disease prevention but they are also technically difficult targets.Part of our work is also directed towards the isolation and characterization of snake venom proteins that interact with platelet receptors and their development as tools.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
63868 Studies on platelet glycoproteins in relation to haemostasis and thrombosis 01.04.2001 Project funding (Div. I-III)

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