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

Autor: Ola Kleveland, Aroon D. Hingorani, Ruth C. Lovering, Rune Wiseth, Jutta Palmen, Juan P. Casas, Jan Kristian Damås, Jorgen Engmann, Marc J. George, Pål Aukrust, Lars Gullestad, Jorge Garcia-Hernandez, Thor Ueland
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Proteomics
Time Factors
Proteome
030204 cardiovascular system & hematology
chemistry.chemical_compound
0302 clinical medicine
Clinical Studies
ST segment
Myocardial infarction
Non-ST Elevated Myocardial Infarction
Randomized Controlled Trials as Topic
Original Research
0303 health sciences
Membrane Glycoproteins
biology
Norway
interleukin
Interleukin
Blood Proteins
Aptamers
Nucleotide
Middle Aged
Treatment Outcome
myocardial infarction
Chemokines
CC
Cardiology
Female
medicine.symptom
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Myeloblastin
Inflammation
Antibodies
Monoclonal
Humanized
03 medical and health sciences
Tocilizumab
Hepcidins
Internal medicine
medicine
Genetics
Humans
Interleukin 6
030304 developmental biology
Aged
business.industry
medicine.disease
Receptors
Interleukin-6
High-Throughput Screening Assays
chemistry
Insulin-Like Growth Factor Binding Protein 4
inflammation
Heart failure
biology.protein
Antagonism
business
Carrier Proteins
Acute-Phase Proteins
Follow-Up Studies
Zdroj: Journal of the American Heart Association
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: 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 SOMA scan 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 SOMA scan 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 SOMA scan 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 .
Databáze: OpenAIRE
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