PhD Defence Claudia Schönichen

Supervisor: Prof. dr. Johan W.M. Heemskerk

Co-supervisors: Prof. dr. Kerstin Jurk, Dr. M.J.E. Kuijpers

Keywords: Platelets, thrombo-inflammation, endothelial inflammation, cell signalling 
 

"A jack of all trades: Platelets at the interface of endothelial inflammation and coagulation"


Platelets are essential for preventing bleeding, but in cardiovascular and inflammatory disorders, their dysregulation increases thrombotic risks. Beyond their clotting role, platelets function as immune cells, offering novel therapeutic targets. This research explores the interactions of activated platelets in thrombosis, immune function, and endothelial inflammation. 

First, using an in vitro arterial thrombosis model, it was found that activated integrin αIIbβ3 suppressed neutrophil adhesion, while platelet CD40L influenced neutrophil movement. Chemokines from platelets triggered calcium signaling in neutrophils, blocked by prostacyclin. Activated neutrophils formed neutrophil extracellular traps (NETs) only under specific conditions. 

Second, the study examined store-operated calcium entry (SOCE) in platelets, regulated by ORAI1 channels and influenced by PKC isoforms. Genetic defects in SOCE components impaired calcium signalling.

Finally, endothelial cells were studied to uncover their role in platelet regulation. Inflammatory stimuli disrupted endothelial antithrombotic mechanisms, altering platelet activation and coagulation pathways. 

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