Interleukin-1ß Mediates Arterial Thrombus Formation via NET-Associated Tissue Factor.
J Clin Med
; 8(12)2019 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-31779200
ABSTRACT
CANTOS reported reduced secondary atherothrombotic events in patients with residual inflammatory risk treated with the inhibitory anti-IL-1ß 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-1ß, 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-1ß, NETosis, and NET-associated TF plasma levels compared with low CRP ones. Additionally, analysis of patients stratified by circulating IL-1ß 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-1ß 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.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article