title: Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size.
abstract: Mechanisms of coronary occlusion in ST-elevation acute coronary syndrome are poorly understood. We have previously reported that neutrophil (polymorphonuclear cells [PMNs]) accumulation in culprit lesion site (CLS) thrombus is a predictor of cardiovascular outcomes.
  
  
  
  The goal of this study was to characterize PMN activation at the CLS. We examined the relationships between CLS neutrophil extracellular traps (NETs), bacterial components as triggers of NETosis, activity of endogenous deoxyribonuclease, ST-segment resolution, and infarct size.
  
  
  
  We analyzed coronary thrombectomies from 111 patients with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention. Thrombi were characterized by immunostaining, flow cytometry, bacterial profiling, and immunometric and enzymatic assays. Compared with femoral PMNs, CLS PMNs were highly activated and formed aggregates with platelets. Nucleosomes, double-stranded DNA, neutrophil elastase, myeloperoxidase, and myeloid-related protein 8/14 were increased in CLS plasma, and NETs contributed to the scaffolds of particulate coronary thrombi. Copy numbers of Streptococcus species correlated positively with dsDNA. Thrombus NET burden correlated positively with infarct size and negatively with ST-segment resolution, whereas CLS deoxyribonuclease activity correlated negatively with infarct size and positively with ST-segment resolution. Recombinant deoxyribonuclease accelerated the lysis of coronary thrombi ex vivo.
  
  
  
  PMNs are highly activated in ST-elevation acute coronary syndrome and undergo NETosis at the CLS. Coronary NET burden and deoxyribonuclease activity are predictors of ST-segment resolution and myocardial infarct size.
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Mangold
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Sherin
authors.initials: S
authors.lastname: Alias
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Scherz
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Thomas
authors.initials: M
authors.lastname: Hofbauer
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Johannes
authors.initials: J
authors.lastname: Jakowitsch
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Adelheid
authors.initials: A
authors.lastname: Panzenböck
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Simon
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Daniela
authors.initials: D
authors.lastname: Laimer
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Christine
authors.initials: C
authors.lastname: Bangert
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Kammerlander
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Julia
authors.initials: J
authors.lastname: Mascherbauer
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Max-Paul
authors.initials: MP
authors.lastname: Winter
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Klaus
authors.initials: K
authors.lastname: Distelmaier
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.).
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.affiliation: From the Division of Cardiology, Department of Internal Medicine II (A.M., S.A., T.S., T.H., J.J., A.P., D.S., A.K., J.M., M.-P.W., K.D., C.A., I.M.L.), Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology (D.L., C.B.), Vienna General Hospital, Medical University of Vienna, Austria; and Institute for Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany (K.T.P.). irene.lang@meduniwien.ac.at.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D054058:Acute Coronary Syndrome / Q000201:enzymology / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D003131:Combined Modality Therapy; D003328:Coronary Thrombosis / Q000201:enzymology / Q000382:microbiology / Q000473:pathology* / Q000601:surgery; D004269:DNA, Bacterial / Q000032:analysis; D003851:Deoxyribonucleases / Q000502:physiology* / Q000627:therapeutic use; D004562:Electrocardiography; D065206:Extracellular Traps / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology*; D020556:Neutrophil Infiltration; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation; D013291:Streptococcus / Q000235:genetics / Q000302:isolation & purification; D017131:Thrombectomy; D015912:Thrombolytic Therapy; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis
chemical_list: D015703:Antigens, CD; D004269:DNA, Bacterial; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D003851:Deoxyribonucleases
keywords: atherosclerosis; coronary occlusion; coronary thrombosis; deoxyribonucleases; extracellular traps; myocardial infarction; neutrophils