20 research outputs found
Novel Insights Into the Effects of Interleukin 6 Antagonism in NonâSTâSegmentâElevation Myocardial Infarction Employing the SOMAscan Proteomics Platform
Background: Interleukin 6 concentration is associated with myocardial injury, heart failure, and mortality after myocardial infarction. In the Norwegian tocilizumab nonâSTâsegmentâelevation myocardial infarction trial, the first randomized trial of interleukin 6 blockade in myocardial infarction, concentration of both Câreactive protein and troponin T were reduced in the active treatment arm. In this followâup study, an aptamerâbased 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 interventionâtreated patients, 24 in the active intervention and 24 in the placeboâcontrol arm, drawn 48 hours postrandomization were randomly selected for analysis with the SOMAscan assay. Employing slow offârate 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 1â3 [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 acuteâphase proteins lipopolysaccharideâbinding protein, hepcidin, and insulinâlike growth factorâbinding protein 4 were all reduced during the hospitalization phase, as was the monocyte chemoattractant CâC motif chemokine ligand 23. Proteinase 3, released primarily from neutrophils, was significantly elevated. /
Conclusions: Employing the SOMAscan aptamerâbased proteomics platform, 5 proteins were newly identified that are modulated by interleukin 6 antagonism and may mediate the therapeutic effects of tocilizumab in nonâSTâsegmentâelevation myocardial infarction