Nieuws

Gina Perrella ontvangt € 375,- vanuit HON voor haar proefschrift

Hart Onderzoek Nederland heeft een bijdrage mogen leveren aan het proefschrift van Gina Perrella, getiteld: ‘Platelet glycoprotein VI in the regulation of thrombus growth’.

GPVI is the principal signalling receptor for collagen, which is exposed upon damage to the extracellular matrix and at site of rupture of an atherosclerotic plaque. GPVI has recently been shown to be also a receptor for fibrinogen and fibrin, which mediate platelet aggregation and clot formation. In mice, GPVI deficiency protects form arterial thrombosis without causing excessive bleeding. Individuals with an inherited deficiency in GPVI have a mild bleeding diathesis. Together, these observations suggest a more important role of GPVI in thrombosis over haemostasis and thus, that GPVI is a potential anti-thrombotic target.

In my thesisI explored the role of GPVI in platelets adhesion to collagen using blood from Chilean patients with a homozygous insertion mutation in the GP6 gene which causes lack of GPVI expression on the platelet surface. I then investigated the contribution of GPVI to platelet adhesion and thrombus growth on fibrin, fibrinogen, using the Syk inhibitor, PRT-060318, and an anti- GPVI Fab, 9O12. Finally, I explored the contribution of GPVI and integrin αIIbβ3 to the stability of a preformed thrombus under flow conditions.

Overall, the research in my thesis provides evidence that the role of GPVI extends beyond the onset of thrombus formation. GPVI activation in response to fibrin(ogen) contributes to platelet aggregation and it is key to thrombus stability. This conclusion further supports the argument that blocking GPVI may effectively prevent arterial thrombosis. Furthermore, this research highlights the importance of the integrin αIIbβ3 in supporting GPVI activation, suggesting that blocking signalling downstream both receptors, can provide an alternative therapeutic strategy for the treatment of arterial thrombosis.

Promovendus: Gina Pirella
Universiteit: Universiteit van Maastricht

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