Novel Insights Into the Effects of Interleukin 6 Antagonism in Non-ST-Segment-Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform.
Acute-Phase Proteins
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Aptamers, Nucleotide
Blood Proteins
/ metabolism
Carrier Proteins
/ blood
Chemokines, CC
/ blood
Female
Follow-Up Studies
Hepcidins
/ blood
High-Throughput Screening Assays
Humans
Insulin-Like Growth Factor Binding Protein 4
/ blood
Male
Membrane Glycoproteins
/ blood
Middle Aged
Myeloblastin
/ blood
Non-ST Elevated Myocardial Infarction
/ blood
Norway
Proteome
Proteomics
Randomized Controlled Trials as Topic
Receptors, Interleukin-6
/ antagonists & inhibitors
Time Factors
Treatment Outcome
inflammation
interleukin
myocardial infarction
proteomics
Journal
Journal of the American Heart Association
ISSN: 2047-9980
Titre abrégé: J Am Heart Assoc
Pays: England
ID NLM: 101580524
Informations de publication
Date de publication:
16 06 2020
16 06 2020
Historique:
pubmed:
10
6
2020
medline:
9
3
2021
entrez:
10
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32515246
doi: 10.1161/JAHA.119.015628
pmc: PMC7429051
doi:
Substances chimiques
Acute-Phase Proteins
0
Antibodies, Monoclonal, Humanized
0
Aptamers, Nucleotide
0
Blood Proteins
0
CCL23 protein, human
0
Carrier Proteins
0
Chemokines, CC
0
HAMP protein, human
0
Hepcidins
0
IGFBP4 protein, human
0
IL6R protein, human
0
Insulin-Like Growth Factor Binding Protein 4
0
Membrane Glycoproteins
0
Proteome
0
Receptors, Interleukin-6
0
lipopolysaccharide-binding protein
0
Myeloblastin
EC 3.4.21.76
tocilizumab
I031V2H011
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e015628Subventions
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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