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Platelet cAMP signalling controls thrombosis through enhanced embolisation

People Involved

Dr Simon Calaminus

Project Description

The activation of protein kinase A (PKA) by prostacyclin inhibits platelet activation and therefore modulates arterial thrombosis. However, the role of PKA in controlling the stability of pre-existing thrombi is unclear. The stability of thrombi is reliant on the correct activation of the platelet actin cytoskeleton by a number of RhoGTPases. We have shown recently that PKA inhibits the activation of the small RhoGTPase RhoA, which blocks actin remodelling. We now have preliminary data that suggest PKA can reverse stress fibre formation, which is required for thrombus stabilisation. We hypothesise that PKA signaling can reverse actin restructuring in thrombus localised platelets, reducing thrombus structural integrity and promoting embolisation as a mechanism to control thrombus size. Data from this study will reveal new insights into the role of PKA signaling in platelets and demonstrate that PKA plays a dual role both in platelet inhibition prior to thrombus formation, but also in limiting the overall size of a thrombus by modulation of the platelet cytoskeleton.

Type of Project Project
Status Project Complete
Funder(s) British Heart Foundation
Value £106,467.00
Project Dates Oct 1, 2015 - Sep 30, 2018

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