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Open AccessArticle

Interleukin-1β Mediates Arterial Thrombus Formation via NET-Associated Tissue Factor

Center for Molecular Cardiology, Schlieren Campus, University of Zurich, 8952 Schlieren, Switzerland
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
Department of Cardiology, University Hospital Zurich, 8091 Zurich, Switzerland
Department of Internal Medicine, Cantonal Hospital of Baden, 5404 Baden, Switzerland
Department of Cardiology, Hopital Universitaire de Geneve, 1206 Geneve, Switzerland
IRCCS Ospedale Policlinico San Martino Genoa—Italian Cardiovascular Network, 16132 Genoa, Italy
Department of Research and Education, University Hospital Zurich, 8001 Zurich, Switzerland
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 02115 Boston, MA, USA
Royal Brompton and Harefield Hospitals and Imperial College, London SW3 6NP, UK
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(12), 2072;
Received: 4 November 2019 / Revised: 19 November 2019 / Accepted: 21 November 2019 / Published: 26 November 2019
CANTOS reported reduced secondary atherothrombotic events in patients with residual inflammatory risk treated with the inhibitory anti-IL-1β antibody, Canakinumab. Yet, mechanisms that underlie this benefit remain elusive. Recent work has implicated formation of neutrophil extracellular traps (NETosis) in arterial thrombosis. Hence, the present study explored the potential link between IL-1β, NETs, and tissue factor (TF)—the key trigger of the coagulation cascade—in atherothrombosis. To this end, ST-elevation myocardial infarction (STEMI) patients from the Swiss multicenter trial SPUM-ACS were retrospectively and randomly selected based on their CRP levels. In particular, 33 patients with STEMI and high C-reactive protein (CRP) levels (≥ 10 mg/L) and, 33 with STEMI and low CRP levels (≤ 4 mg/L) were investigated. High CRP patients displayed elevated circulating IL-1β, NETosis, and NET-associated TF plasma levels compared with low CRP ones. Additionally, analysis of patients stratified by circulating IL-1β levels yielded similar results. Moreover, NETosis and NET-associated TF plasma levels correlated positively in the whole population. In addition to the above, translational research experiments provided mechanistic confirmation for the clinical data identifying IL-1β as the initial trigger for the release of the pro-coagulant, NET-associated TF. In conclusion, blunted TF presentation by activated neutrophils undergoing NETosis may provide a mechanistic explanation to reduced secondary atherothrombotic events as observed in canakinumab-treated patients in CANTOS. View Full-Text
Keywords: IL-1β; Canakinumab; arterial thrombosis; tissue factor; neutrophil extracellular traps IL-1β; Canakinumab; arterial thrombosis; tissue factor; neutrophil extracellular traps
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Liberale, L.; Holy, E.W.; Akhmedov, A.; Bonetti, N.R.; Nietlispach, F.; Matter, C.M.; Mach, F.; Montecucco, F.; Beer, J.H.; Paneni, F.; Ruschitzka, F.; Libby, P.; Lüscher, T.F.; Camici, G.G. Interleukin-1β Mediates Arterial Thrombus Formation via NET-Associated Tissue Factor. J. Clin. Med. 2019, 8, 2072.

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