{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liberale L"],"funding":["American Heart Association","National Heart and Lung Institute"],"pagination":["E2072"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6947515"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(12)"],"pubmed_abstract":["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."],"journal":["Journal of clinical medicine"],"pubmed_title":["Interleukin-1β Mediates Arterial Thrombus Formation via NET-Associated Tissue Factor."],"pmcid":["PMC6947515"],"funding_grant_id":["R01HL134892","18CSA34080399","R01HL080472"],"pubmed_authors":["Akhmedov A","Matter CM","Bonetti NR","Luscher TF","Holy EW","Liberale L","Camici GG","Ruschitzka F","Mach F","Libby P","Beer JH","Montecucco F","Paneni F","Nietlispach F"],"additional_accession":[]},"is_claimable":false,"name":"Interleukin-1β Mediates Arterial Thrombus Formation via NET-Associated Tissue Factor.","description":"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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Nov","modification":"2024-11-11T22:26:04.159Z","creation":"2020-05-22T07:44:47Z"},"accession":"S-EPMC6947515","cross_references":{"pubmed":["31779200"],"doi":["10.3390/jcm8122072"]}}