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Open AccessArticle

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

1
Center for Molecular Cardiology, Schlieren Campus, University of Zurich, 8952 Schlieren, Switzerland
2
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
3
Department of Cardiology, University Hospital Zurich, 8091 Zurich, Switzerland
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Department of Internal Medicine, Cantonal Hospital of Baden, 5404 Baden, Switzerland
5
Department of Cardiology, Hopital Universitaire de Geneve, 1206 Geneve, Switzerland
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IRCCS Ospedale Policlinico San Martino Genoa—Italian Cardiovascular Network, 16132 Genoa, Italy
7
Department of Research and Education, University Hospital Zurich, 8001 Zurich, Switzerland
8
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 02115 Boston, MA, USA
9
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; https://doi.org/10.3390/jcm8122072
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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