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

Luca Liberale, Erik W Holy, Alexander Akhmedov, Nicole R Bonetti, Fabian Nietlispach, Christian M Matter, François Mach, Fabrizio Montecucco, Jürg H Beer, Francesco Paneni, Frank Ruschitzka, Peter Libby, Thomas F Lüscher, Giovanni G Camici

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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.

Original languageEnglish
JournalJournal of Clinical Medicine
Issue number12
Publication statusPublished - Nov 26 2019


Cite this

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. (2019). Interleukin-1β Mediates Arterial Thrombus Formation via NET-Associated Tissue Factor. Journal of Clinical Medicine, 8(12).