Platelet Activation in Vascular Disease: from Animal Studies to Clinical Consequences

Abstract

The zebrafish is an in vivo model system originally used to study development of vertebrates. Over the last years it has gained a more important role in studies focusing on diseases such as cancer and thrombosis. Platelets play an important role in thrombosis and therefore drugs inhibiting platelet enzymes and receptors are developed to prevent thrombosis. The most effective drugs inhibit the COX enzymes (aspirin) or the platelet activating receptor P2Y-12 (clopidogrel among others). Lack of clarity exists about the P2Y12 receptor. In T2DM patients, there is speculation that there is less inhibition by 16 antagonists. Also the current insight in P2Y12 signaling is limited to suppression of production of cAMP (a platelet inhibitor) and activation of protein kinase B/Rap1b (which stimulate aggregation). Aims of the thesis: (1) To evaluate the position of the zebrafish as a model system in research on platelet function and thrombus; (2) Discuss the main problems the currently most used anti-platelet drugs (aspirin and clopidogrel) possess; (3) To study the inhibition of the P2Y-12 receptor in diabetes patients and to demonstrate which secondary signalling molecules are activated by P2Y-1