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 P, Klingel K, Sauter M, Westermann D, Ochmann C, Schönberger T, Schleicher R, Stellos K, Schmidt EM, Borst O, Bigalke B, Kandolf R, Langer H, Gawaz M, May AE
  (See online at https://doi.org/10.1016/j.yjmcc.2012.03.004)
• EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory cardiomyopathy. Int J Cardiol. 2013 Mar 10;163(3):299-304
  Seizer P, Geisler T, Bigalke B, Schneider M, Klingel K, Kandolf R, Stellos K, Schreieck J, Gawaz M, May AE
  (See online at https://doi.org/10.1016/j.ijcard.2011.06.049)
• 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 P, von Ungern-Sternberg SN, Schönberger T, Borst O, Münzer P, Schmidt EM, Mack AF, Heinzmann D, Chatterjee M, Langer H, Malešević M, Lang F, Gawaz M, Fischer G, May AE
  (See online at https://doi.org/10.1161/atvbaha.114.305112)
• Regulation of EMMPRIN (CD147) on monocyte subsets in patients with symptomatic coronary artery disease. Thromb Res. 2015;Jun;135(6):1160-4
  Sturhan H, von Ungern-Sternberg SN, Langer H, Gawaz M, Geisler T, May AE, Seizer P
  (See online at https://doi.org/10.1016/j.thromres.2015.03.022)
• 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 D, Bangert A, Müller AM, von Ungern-Sternberg SN, Emschermann F, Schönberger T, Chatterjee M, Mack AF, Klingel K, Kandolf R, Malesevic M, Borst O, Gawaz M, Langer HF, Katus H, Fischer G, May AE, Kaya Z, Seizer P
  (See online at https://doi.org/10.1371/journal.pone.0124606)
• Platelet-bound cyclophilin A in patients with stable coronary artery disease and acute myocardial infarction. Platelets 2016;27(2):155-8
  Seizer P, Fuchs C, von Ungern-Sternberg SN, Heinzmann D, Langer H, Gawaz M, May AE, Geisler T
  (See online at https://doi.org/10.3109/09537104.2015.1051466)
• Extracellular Cyclophilin A Augments Platelet-Dependent Thrombosis and Thromboinflammation. Thromb Haemost. 2017;Nov;117(11):2063-2078
  von Ungern-Sternberg SN, Vogel S, Walker-Allgaier B, Geue S, Maurer A, Wild AM, Münzer P, Chatterjee M, Heinzmann D, Kremmer E, Borst O, Loughran P, Zernecke A, Neal MD, Billiar TR, Gawaz M, Seizer P
  (See online at https://doi.org/10.1160/th17-01-0067)
• S100A9 induces monocyte/ macrophage migration via EMMPRIN. Thromb Haemost. 2017;Feb 28;117(3):636-639
  Alexaki VI, May AE, Fujii C, von Ungern-Sternberg SN, Mund C, Gawaz M, Chavakis T, Seizer P
  (See online at https://doi.org/10.1160/th16-06-0434)
• 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 D, Fuß S, von Ungern-Sternberg SN, Schreieck J, Gawaz M, Gramlich M, Seizer P
  (See online at https://doi.org/10.1159/000492873)