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

Final Report Abstract

Platelets are a central player in the regulation of inflammatory processes. During activation platelets are able to release inflammatory mediators like Danger Associated Molecular Patterns (DAMPs). Cyclophilin A (CyPA) is a DAMP which is released from platelets. This extracellular CyPA is binding to the already known receptor Extracellular Matrix MetalloProteinase Inducer (EMMPRIN, CD147).

Publications

• Cyclophilin A affects inflammation, virus elimination and myocardial fibrosis in coxsackievirus B3-induced myocarditis. J Mol Cell Cardiol. 2012;Jul;53(1):6-14
  Seizer, Peter; Klingel, Karin; Sauter, Martina; Westermann, Dirk; Ochmann, Carmen; Schönberger, Tanja; Schleicher, Rebecca; Stellos, Konstantinos; Schmidt, Eva-Maria; Borst, Oliver; Bigalke, Boris; Kandolf, Reinhard; Langer, Harald; Gawaz, Meinrad & May, Andreas E.
  
• EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory cardiomyopathy. Int J Cardiol. 2013 Mar 10;163(3):299-304
  Seizer, Peter; Geisler, Tobias; Bigalke, Boris; Schneider, Martin; Klingel, Karin; Kandolf, Reinhard; Stellos, Konstantinos; Schreieck, Jürgen; Gawaz, Meinrad & May, Andreas E.
  
• Extracellular cyclophilin A activates platelets via EMMPRIN (CD147) and PI3K/Akt signaling, which promotes platelet adhesion and thrombus formation in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2015;Mar;35(3):655-63
  Seizer, Peter; Ungern-Sternberg, Saskia N.I.v.; Schönberger, Tanja; Borst, Oliver; Münzer, Patrick; Schmidt, Eva-Maria; Mack, Andreas F.; Heinzmann, David; Chatterjee, Madhumita; Langer, Harald; Malešević, Miroslav; Lang, Florian; Gawaz, Meinrad; Fischer, Gunter & May, Andreas E.
  
• Platelet-bound cyclophilin A in patients with stable coronary artery disease and acute myocardial infarction. Platelets 2016;27(2):155-8
  Seizer, Peter; Fuchs, Christian; Ungern-Sternberg, Saskia N.I. v.; Heinzmann, David; Langer, Harald; Gawaz, Meinrad; May, Andreas E. & Geisler, Tobias
  
• Regulation of EMMPRIN (CD147) on monocyte subsets in patients with symptomatic coronary artery disease. Thromb Res. 2015;Jun;135(6):1160-4
  Sturhan, Henrik; Ungern-Sternberg, Saskia N.I.v.; Langer, Harald; Gawaz, Meinrad; Geisler, Tobias; May, Andreas E. & Seizer, Peter
  
• The Novel Extracellular Cyclophilin A (CyPA) - Inhibitor MM284 Reduces Myocardial Inflammation and Remodeling in a Mouse Model of Troponin I -Induced Myocarditis. PLoS One 2015;Apr 20;10(4):e0124606
  Heinzmann, David; Bangert, Anna; Müller, Anna-Maria; von Ungern-Sternberg, Saskia N. I.; Emschermann, Frederic; Schönberger, Tanja; Chatterjee, Madhumita; Mack, Andreas F.; Klingel, Karin; Kandolf, Reinhard; Malesevic, Miroslav; Borst, Oliver; Gawaz, Meinrad; Langer, Harald F.; Katus, Hugo; Fischer, Gunter; May, Andreas E.; Kaya, Ziya & Seizer, Peter
  
• Extracellular Cyclophilin A Augments Platelet-Dependent Thrombosis and Thromboinflammation. Thromb Haemost. 2017;Nov;117(11):2063-2078
  von Ungern-Sternberg, Saskia; Vogel, Sebastian; Walker-Allgaier, Britta; Geue, Sascha; Maurer, Andreas; Wild, Anna-Maria; Münzer, Patrick; Chatterjee, Madhumita; Heinzmann, David; Kremmer, Elisabeth; Borst, Oliver; Loughran, Patricia; Zernecke, Alma; Neal, Matthew; Billiar, Timothy; Gawaz, Meinrad & Seizer, Peter
  
• S100A9 induces monocyte/ macrophage migration via EMMPRIN. Thromb Haemost. 2017;Feb 28;117(3):636-639
  Alexaki, Vasileia Ismini; May, Andreas E.; Fujii, Chika; Mund, Christine; Gawaz, Meinrad; Ungern-Sternberg, Saskia N. I. v.; Chavakis, Triantafyllos & Seizer, Peter
  
• TGFβ Is Specifically Upregulated on Circulating CD14++ CD16+ and CD14+ CD16++ Monocytes in Patients with Atrial Fibrillation and Severe Atrial Fibrosis. Cell Physiol Biochem. 2018;49(1):226-234
  Heinzmann, David; Fuß, Stefan; Ungern-Sternberg, Saskia v.; Schreieck, Jürgen; Gawaz, Meinrad; Gramlich, Michael & Seizer, Peter