Neutrophil Extracellular Traps in ST-Segment Elevation Myocardial Infarction

Kristine Mørk Kindberg, MD; Kaspar Broch, MD, PhD; Geir Øystein Andersen, MD, PhD; Anne Kristine Anstensrud, MD; Sissel Åkra, MSc; Sindre Woxholt, MD; Ingvild Maria Tøllefsen, MD, PhD; Thor Ueland, PhD; Brage Høyem Amundsen, MD, PhD; Nils-Einar Kløw, MD, PhD; Bente Halvorsen, MSc, PhD; Tuva B. Dahl, MSc, PhD; Camilla Huse, PhD; Sarah Louise Murphy, MSc; Jan Kristian Damås, MD, PhD; Anders Opdahl, MD, PhD; Rune Wiseth, MD, PhD; Lars Gullestad, MD, PhD; Pål Aukrust, MD, PhD; Carlos Santos-Gallego, MD; Ingebjørg Seljeflot, PhD; Mathis Korseberg Stokke, MD, PhD; Ragnhild Helseth, MD, PhD

JACC: Advances (Sep 2024)

Neutrophil Extracellular Traps in ST-Segment Elevation Myocardial Infarction

Kristine Mørk Kindberg, MD,
Kaspar Broch, MD, PhD,
Geir Øystein Andersen, MD, PhD,
Anne Kristine Anstensrud, MD,
Sissel Åkra, MSc,
Sindre Woxholt, MD,
Ingvild Maria Tøllefsen, MD, PhD,
Thor Ueland, PhD,
Brage Høyem Amundsen, MD, PhD,
Nils-Einar Kløw, MD, PhD,
Bente Halvorsen, MSc, PhD,
Tuva B. Dahl, MSc, PhD,
Camilla Huse, PhD,
Sarah Louise Murphy, MSc,
Jan Kristian Damås, MD, PhD,
Anders Opdahl, MD, PhD,
Rune Wiseth, MD, PhD,
Lars Gullestad, MD, PhD,
Pål Aukrust, MD, PhD,
Carlos Santos-Gallego, MD,
Ingebjørg Seljeflot, PhD,
Mathis Korseberg Stokke, MD, PhD,
Ragnhild Helseth, MD, PhD

Affiliations

Kristine Mørk Kindberg, MD: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Address for correspondence: Dr Kristine Mørk Kindberg, Department of Cardiology, Oslo University Hospital Ullevål, 0455 Oslo, Norway.
Kaspar Broch, MD, PhD: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway
Geir Øystein Andersen, MD, PhD: Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway
Anne Kristine Anstensrud, MD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
Sissel Åkra, MSc: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway
Sindre Woxholt, MD: Clinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Ingvild Maria Tøllefsen, MD, PhD: Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway
Thor Ueland, PhD: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Thrombosis Research and Expertise Center (TREC), The Arctic University of Norway, Tromsø, Norway
Brage Høyem Amundsen, MD, PhD: Clinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Nils-Einar Kløw, MD, PhD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Radiology, Oslo University Hospital Ullevaal, Oslo, Norway
Bente Halvorsen, MSc, PhD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Tuva B. Dahl, MSc, PhD: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Camilla Huse, PhD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Sarah Louise Murphy, MSc: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Jan Kristian Damås, MD, PhD: Department of Infectious Disease, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Anders Opdahl, MD, PhD: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
Rune Wiseth, MD, PhD: Clinic of Cardiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Lars Gullestad, MD, PhD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway
Pål Aukrust, MD, PhD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
Carlos Santos-Gallego, MD: AtheroThrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Ingebjørg Seljeflot, PhD: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Mathis Korseberg Stokke, MD, PhD: Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway
Ragnhild Helseth, MD, PhD: Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital Ullevaal, Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway

Journal volume & issue: Vol. 3, no. 9
p. 101193

Abstract

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Background: Interleukin-6-receptor inhibition with tocilizumab improves myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI). Reduced levels of neutrophil extracellular traps (NETs), which consist of nuclear material studded with proteins released upon neutrophil activation, might contribute to this effect. Objectives: The purpose of this study was to evaluate the effect of tocilizumab on NETs and investigate the association between NETs and myocardial injury in patients with STEMI. Methods: In the ASSAIL-MI study, 199 patients with STEMI were randomized to tocilizumab or placebo during percutaneous coronary intervention. In this substudy, we analyzed blood levels of the NET markers double-stranded deoxyribonucleic acid (dsDNA), myeloperoxidase-DNA, and citrullinated histone 3 (H3Cit) at admission and after 24 hours and 3 to 7 days. In a subgroup of patients, we assessed regulation of transcripts related to the formation of NETs. We also investigated associations between NET markers and the myocardial salvage index (MSI). Results: All NET markers were lower in the tocilizumab group than in the placebo group at 3 to 7 days (all P < 0.04). Several NET-related pathways were downregulated in the tocilizumab group. The beneficial effect of tocilizumab on the MSI seemed to be partly dependent on reduction of NETs (structural equation modeling: 0.05, P = 0.001 [dsDNA] and 0.02, P = 0.055 [H3Cit]). Patients with NETs in the 3 lowest quartiles had higher MSI than patients in quartile 4 (10.9 [95% CI: 4.0-15.0] [dsDNA] and 8.9 [95% CI: 2.0-15.9] [H3Cit], both P = 0.01). Conclusions: NETs were reduced by tocilizumab and associated with myocardial injury. The effect of tocilizumab on MSI might be mediated through reduced NETs. (ASSessing the Effect of Anti-IL-6 Treatment in Myocardial Infarction: The ASSAIL-MI Trial [ASSAIL-MI]; NCT03004703)

Published in JACC: Advances

ISSN: 2772-963X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://www.sciencedirect.com/journal/jacc-advances

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