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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Published in:	Basic research in cardiology Vol. 119; no. 3; pp. 453 - 479
Main Authors:	Schnitter, Florian, Stangl, Franziska, Noeske, Elisabeth, Bille, Maya, Stadtmüller, Anja, Vogt, Niklas, Sicklinger, Florian, Leuschner, Florian, Frey, Anna, Schreiber, Laura, Frantz, Stefan, Beyersdorf, Niklas, Ramos, Gustavo, Gladow, Nadine, Hofmann, Ulrich
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-06-2024 Springer Nature B.V
Subjects:	Animal models Animals Balloon treatment Cardiology CD4 antigen Disease Models, Animal Extracellular matrix Female Flow cytometry Foxp3 protein Gene sequencing Heart Heart attacks Helper cells Histology Immune response Immune system Immunoregulation Immunotherapy Inflammation Leukocytes Lymph nodes Lymphocyte Activation Lymphocytes Lymphocytes T Male Medicine Medicine & Public Health Myeloid cells Myelopoiesis Myocardial infarction Myocardial Infarction - immunology Myocardial Infarction - pathology Myocardium Myocardium - immunology Myocardium - pathology Occlusion Original Contribution Sus scrofa Swine T-Lymphocytes, Regulatory - immunology Time Factors Transcriptome Transcriptomes Myocardial infarction Heart Immunophenotyping Leukocytes Swine Pig
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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 (T reg ), 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 T reg 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1435-1803 0300-8428 1435-1803
DOI:	10.1007/s00395-024-01036-2