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01.01.2019 | Original Contribution | Ausgabe 1/2019 Open Access

Basic Research in Cardiology 1/2019

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

Zeitschrift:
Basic Research in Cardiology > Ausgabe 1/2019
Autoren:
Ellis N. ter Horst, Paul A. J. Krijnen, Nazanin Hakimzadeh, Lourens F. H. J. Robbers, 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 Schoot, Tineke C. T. M. van der Pouw Kraan, Anton J. Horrevoets, Anja M. van der Laan, Hans W. M. Niessen, Jan J. Piek
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00395-018-0709-7) contains supplementary material, which is available to authorized users.

Abstract

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

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Supplementary material 1 (DOCX 274 kb)
395_2018_709_MOESM1_ESM.docx
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