Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats

• DOI: 10.1007/s00395-018-0709-7
• Publication Date: 2018-11-12T09:17:55Z
• Authors: Ellis N. ter Horst; Paul A. J. Krijnen; Nazanin Hakimzadeh; Lourens F. H. J. ...; Alexander Hirsch; Robin Nijveldt; Ingrid Lommerse; Ruud D. Fontijn; Elisa Meinster; Ronak Delewi; Niels van Royen; Felix Zijlstra; Albert C. van Rossum; C. Ellen van der ...; Tineke C. T. M. v...; Anton J. Horrevoets; Anja M. van der Laan; Hans W. M. Niessen; Jan J. Piek
• Keywords: Monocyte; Ventricular remodeling; CD68

Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provide therapeutic opportunities we aimed to identify gene transcripts monocytes that relate post-MI healing and evaluated intervention with the observed activity a rat MI model. In 51 patients treated by primary percutaneous coronary (PCI), change LV end-diastolic volume index (EDVi) from baseline 4-month follow-up was assessed using cardiovascular magnetic resonance imaging (CMR). Circulating were collected at day 5 (Arterioscler Thromb Vasc Biol 35:1066–1070, 2015; Cell Stem 16:477–487, Curr Med Chem 13:1877–1893, 2006) after PCI for transcriptome analysis. Transcriptional profiling pathway analysis revealed decreased EDVi showed an induction of type I interferon (IFN) signalling (type IFN pathway: P value < 0.001; false discovery rate 0.001). We subsequently administered 15,000 Units IFN-α subcutaneously model three consecutive days MI. Cardiac function measured echocardiography infarct size/cardiac inflammation (immuno)-histochemical found application deteriorated dilatation increased size 28 post-MI. Moreover, changed peripheral monocyte subset distribution towards pro-inflammatory whereas myocardium, presence alternative macrophage 3 Our findings suggest human coincides remodelling. rats, however, administration healing. These underscore important but also contradictory roles response during cardiac