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Open Access 01-01-2019 | Original Contribution

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

Authors: 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

Published in: Basic Research in Cardiology | Issue 1/2019

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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Title: 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
Authors: 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
Publication date: 01-01-2019
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 1/2019
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-018-0709-7

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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

Abstract

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Abstract

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ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page