Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.
Basic Res Cardiol
; 117(1): 63, 2022 11 30.
Article
em En
| MEDLINE
| ID: mdl-36449104
ABSTRACT
Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Coração
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Basic Res Cardiol
Ano de publicação:
2022
Tipo de documento:
Article