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Novel Insights Into the Effects of Interleukin 6 Antagonism in Non–ST‐Segment–Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform

George, MJ; Kleveland, O; Garcia-Hernandez, J; Palmen, J; Lovering, R; Wiseth, R; Aukrust, P; ... Ueland, T; + view all (2020) Novel Insights Into the Effects of Interleukin 6 Antagonism in Non–ST‐Segment–Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform. Journal of the American Heart Association , 9 (12) , Article e015628. 10.1161/JAHA.119.015628. Green open access

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Abstract

Background: Interleukin 6 concentration is associated with myocardial injury, heart failure, and mortality after myocardial infarction. In the Norwegian tocilizumab non–ST‐segment–elevation myocardial infarction trial, the first randomized trial of interleukin 6 blockade in myocardial infarction, concentration of both C‐reactive protein and troponin T were reduced in the active treatment arm. In this follow‐up study, an aptamer‐based proteomic approach was employed to discover additional plasma proteins modulated by tocilizumab treatment to gain novel insights into the effects of this therapeutic approach. / Methods and Results: Plasma from percutaneous coronary intervention–treated patients, 24 in the active intervention and 24 in the placebo‐control arm, drawn 48 hours postrandomization were randomly selected for analysis with the SOMAscan assay. Employing slow off‐rate aptamers, the relative abundance of 1074 circulating proteins was measured. Proteins identified as being significantly different between groups were subsequently measured by enzyme immunoassay in the whole trial cohort (117 patients) at all time points (days 1–3 [7 time points] and 3 and 6 months). Five proteins identified by the SOMAscan assay, and subsequently confirmed by enzyme immunoassay, were significantly altered by tocilizumab administration. The acute‐phase proteins lipopolysaccharide‐binding protein, hepcidin, and insulin‐like growth factor‐binding protein 4 were all reduced during the hospitalization phase, as was the monocyte chemoattractant C‐C motif chemokine ligand 23. Proteinase 3, released primarily from neutrophils, was significantly elevated. / Conclusions: Employing the SOMAscan aptamer‐based proteomics platform, 5 proteins were newly identified that are modulated by interleukin 6 antagonism and may mediate the therapeutic effects of tocilizumab in non–ST‐segment–elevation myocardial infarction.

Type: Article
Title: Novel Insights Into the Effects of Interleukin 6 Antagonism in Non–ST‐Segment–Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/JAHA.119.015628
Publisher version: https://doi.org/10.1161/JAHA.119.015628
Language: English
Additional information: Copyright © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: inflammation, interleukin, myocardial infarction, proteomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10101507
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