Role of cyclophilins and other EMMPRIN-ligands for platelet function and platelet-monocyte interaction

• Applicant: Privatdozent Dr. Peter Seizer
• Subject Area: Cardiology, Angiology
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190538538

Platelets are central regulators of inflammatory cardiovascular processes. Upon activation platelets release a variety of pro-inflammatory substances including cyclophilins. Extracellular Cyclophilin A and B can induce proinflammatory pathways in monocytes via the Extracellular Matrix Metallo proteinase Inducer EMMPRIN. In the current funding period we could show that intracellular CyPA is a crucial regulator of platelets Ca2+ homeostasis. Thus, mice lacking CyPA are nearly protected from arterial thrombosis. In addition to its important intracellular role in platelets we could also describe the important influence of extracellular CyPA on platelet activation. Our current preliminary data show that may other receptors than EMMPRIN could be involved in CyPAactivation processes. Furthermore other DAMPs (¿danger associated molecular patterns¿) can bind to EMMPRIN vice versa. In the following funding period they we will characterize these novel interactions and clarify their influence in platelet-monocyte interaction. Finally we intend to evaluate our experimental data in patient cohorts. Based on these findings novel antithrombotic substances could be developed.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 274: Platelets - Molecular Mechanisms and Translational Implications