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

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Clearing the thrombosis pathway

Arterial thrombosis is the first cause of death and ill health in the western world. The aggregation of platelets plays a major role in the development of this pathology, which can lead to heart attacks and strokes.

Health

Although anti-platelet therapies are effectively used for primary and secondary prevention of cardiovascular and cerebrovascular diseases, arterial thrombosis remains a severe health problem. To develop new anti-thrombotic drugs that will lessen associated health risks, we need a better understanding of how platelets are activated. The 'Interaction between major pathways for platelet activation in mouse models of arterial thrombosis' (In vivo thrombosis) project aimed to better define the role of thrombin signalling and to explore how relevant pathways influence a disruption in normal blood flow and thrombosis. This study employed advanced genetic engineering techniques and mouse models of haemostasis and thrombosis. Thrombin is a protease protein that is active in guiding a wide range of coagulation-related reactions. Protease-activated receptor 4 (PAR4) is a protein receptor and powerful mediator of platelet activation and inflammation, especially when alerted to elevated concentrations of thrombin. The objectives of this EU-funded study included identifying pathways triggering the platelet thrombi formation in the absence of PAR4 function. Project partners focused on the interplay between the PAR4-thrombin pathway and the Glycoprotein (GP) VI-collagen pathway. Study results revealed that PAR4 deficiency alone comes with higher bleeding risk, albeit better protection against thrombosis. Combined GPVI and PAR4 deficiency offers better protection against thrombosis but still carries a risk of increased bleeding. Following the logic of combining two anti-platelet drugs, currently standard practice for antithrombotic therapies, project outcomes resulted in greater understanding of bleeding risk and protection against thrombosis. Such new information is significant for professionals working to manage cardiac and neurological diseases.

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