According to the World Health Organisation, cardiovascular diseases are the most common cause of death worldwide. If the finely-tuned cell mechanisms in the vascular system of the body are disrupted, this can promote inflammation and blood coagulation (thromboses). The European joint project »Thromboinflammation in cardiovascular diseases« (TICARDIO) combines the investigations into these two pathological processes for the first time under the heading “Thromboinflammation”. This project focusses on the interaction between the vessel wall and blood, which has a key role to play in the abnormal processes in cardiovascular disease. The aim is to find new target molecules (targets) for active pharmaceutical ingredients and specific diagnostic markers.
Inhibiting and activating paths of blood platelets in thrombosis The endothelial cells produce substances that line the inside of blood vessels and inhibit or activate the thrombocytes. The »TICARDIO« subproject »Endothelial-derived inhibiting and activating pathways of platelets in thrombosis« at ISAS addresses the role this plays in the emergence of thrombosis. A phospho-targeted mass spectrometry-based assay is being used in order, for example, to investigate the key mediators of the inhibiting and activating paths of the thrombocytes. During the course of the project, it has been possible to identify the tyrosine-protein kinase Syk as key mediator, and also verify the total Syk protein and three different phosphorylated points. Phosphorylation, the reversible attachment of a phosphate group, plays an important role in the transmission of cellular signals. The analysis therefore enables conclusions to be drawn about how thrombocytes are inhibited and activated. A further aim is to characterise the variants of the phosphorylation points using ion mobility spectrometry.
About TICARDIO
TICARDIO is an international study which promotes the interdisciplinary training of postgraduates. It offers 15 doctoral candidates of the natural sciences a route to obtaining a European Joint Doctorate. The participants also benefit from the multi-disciplinary and intersectoral collaboration of all organisations involved. The Center for Thrombosis and Haemostasis (CTH) at the University Medical Center in Mainz coordinates the network of doctoral candidates.
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FASEB Journal, Vol. 38, No. 4, 2024, P. e23468
Provenzale I, Solari FA, Schönichen C, Brouns SLN, Fernández DI, Kuijpers MJE, van der Meijden PEJ, Gibbins JM, Sickmann A, Jones C, Heemskerk JWM.
Endothelium-mediated regulation of platelet activation: Involvement of multiple protein kinases
https://doi.org/10.1096/fj.202300360RR
Thrombosis and Haemostasis, Vol. 123, No. 8, 2023, P. 808-839
Akbulut AC, Arisz RA, Baaten CCFMJ, Baidildinova G, Barakzie A, Bauersachs R, Ten Berg J, van den Broek WWA, de Boer HC, Bonifay A, Bröker V, Buka…
Blood Coagulation and Beyond
https://doi.org/10.1055/a-2052-9175
International Journal of Molecular Sciences, Vol. 24, No. 9, 2023
Zhang P, Solari F, Heemskerk JW, Kuijpers MJE, Sickmann A, Walter U, Jurk K.
Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets
https://doi.org/10.3390/ijms24097776
Blood, Vol. 139, No. 17, 2022, P. 2691-2705
Leberzammer J, Agten SM, Blanchet X, Duan R, Ippel H, Megens RTA, Schulz C, Aslani M, Duchene J, Doring Y, Jooss NJ, Zhang P, Brandl R, Stark K,…
Targeting platelet-derived CXCL12 impedes arterial thrombosis
https://doi.org/10.1182/blood.2020010140