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Characterizing the immune response to myocardial infarction in pigs

Though myocardial infarction (MI) in pigs is a well-established translational large animal model, it has not yet been widely used for immunotherapy studies, and a comprehensive description of the immune response to MI in this species is lacking. We induced MI in Landrace pigs by balloon occlusion of...

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Main Authors: Schnitter, Florian (Author) , Stangl, Franziska (Author) , Noeske, Elisabeth (Author) , Bille, Maya (Author) , Stadtmüller, Anja (Author) , Vogt, Niklas (Author) , Sicklinger, Florian (Author) , Leuschner, Florian (Author) , Frey, Anna (Author) , Schreiber, Laura (Author) , Frantz, Stefan (Author) , Beyersdorf, Niklas (Author) , Ramos, Gustavo (Author) , Gladow, Nadine (Author) , Hofmann, Ulrich (Author)
Format: Article (Journal)
Language:English
Published: 15 March 2024
In: Basic research in cardiology
Year: 2024, Volume: 119, Issue: 3, Pages: 453-479
ISSN:1435-1803
DOI:10.1007/s00395-024-01036-2
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00395-024-01036-2
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Author Notes:Florian Schnitter, Franziska Stangl, Elisabeth Noeske, Maya Bille, Anja Stadtmüller, Niklas Vogt, Florian Sicklinger, Florian Leuschner, Anna Frey, Laura Schreiber, Stefan Frantz, Niklas Beyersdorf, Gustavo Ramos, Nadine Gladow, Ulrich Hofmann
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Summary:Though myocardial infarction (MI) in pigs is a well-established translational large animal model, it has not yet been widely used for immunotherapy studies, and a comprehensive description of the immune response to MI in this species is lacking. We induced MI in Landrace pigs by balloon occlusion of the left anterior descending artery over 90 min. Within 14 days, the necrotic myocardium was progressively replaced by scar tissue with involvement of myofibroblasts. We characterized the immune response in the heart ex vivo by (immuno)histology, flow cytometry, and RNA sequencing of myocardial tissue on days 3, 7, and 14 after MI. Besides a clear predominance of myeloid cells among heart-infiltrating leukocytes, we detected activated T cells and an increasing proportion of CD4+ Foxp3+ regulatory T cells (Treg), especially in the infarct core—findings that closely mirror what has been observed in mice and humans after MI. Transcriptome data indicated inflammatory activity that was persistent but markedly changing in character over time and linked to extracellular matrix biology. Analysis of lymphocytes in heart-draining lymph nodes revealed significantly higher proliferation rates of T helper cell subsets, including Treg on day 7 after MI, compared to sham controls. Elevated frequencies of myeloid progenitors in the spleen suggest that it might be a site of emergency myelopoiesis after MI in pigs, as previously shown in mice. We thus provide a first description of the immune response to MI in pigs, and our results can aid future research using the species for preclinical immunotherapy studies.
Item Description:Gesehen am 30.07.2024
Physical Description:Online Resource
ISSN:1435-1803
DOI:10.1007/s00395-024-01036-2

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