title: Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction.
abstract: OBJECTIVE
  Neutrophil extracellular traps (NETs) are chromatin ﬁlaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now.
  
  
  RESULTS
  Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST-segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure.
  
  
  CONCLUSIONS
  The interaction of thrombin-activated platelets with PMNs at the site of plaque rupture during acute STEMI results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets.
authors: Cardiology Department, Democritus University of Thrace, Alexandroupolis, Greece.
authors: Dimitrios A
authors: DA
authors: Stakos
authors: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors: Konstantinos
authors: K
authors: Kambas
authors: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors: Theocharis
authors: T
authors: Konstantinidis
authors: Department of Clinical Pathobiochemistry, and Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine Technische Universität Dresden, Dresden, Germany.
authors: Ioannis
authors: I
authors: Mitroulis
authors: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors: Eirini
authors: E
authors: Apostolidou
authors: Department of Pathology, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors: Stella
authors: S
authors: Arelaki
authors: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors: Victoria
authors: V
authors: Tsironidou
authors: Department of Pathology, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
authors: Alexandra
authors: A
authors: Giatromanolaki
authors: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
authors: Panagiotis
authors: P
authors: Skendros
authors: Cardiology Department, Democritus University of Thrace, Alexandroupolis, Greece Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Stavros
authors: S
authors: Konstantinides
authors: Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece kritis@med.duth.gr.
authors: Konstantinos
authors: K
authors: Ritis
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D003328:Coronary Thrombosis / Q000378:metabolism / Q000601:surgery; D003331:Coronary Vessels / Q000378:metabolism*; D065206:Extracellular Traps / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000601:surgery; D009204:Myocardial Revascularization / Q000379:methods; D009504:Neutrophils / Q000378:metabolism*; D062645:Percutaneous Coronary Intervention; D058226:Plaque, Atherosclerotic; D015539:Platelet Activation / Q000502:physiology; D012422:Rupture, Spontaneous / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D013925:Thromboplastin; D013917:Thrombin
keywords: Inflammation; Myocardial infarction; Neutrophil extracellular traps; Thrombosis; Tissue factor