Publication Date
2-1-2024
Journal
Life Science Alliance
DOI
10.26508/lsa.202201870
PMID
38012001
PMCID
PMC10681909
PubMedCentral® Posted Date
11-27-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Mice, Humans, Animals, Child, Endothelial Cells, Myocardial Infarction, Heart, Heart Failure, Signal Transduction
Abstract
Modulation of the heart’s immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors (Irf7, Batf2, and Stat1). Single-cell chromatin accessibility studies revealed an enrichment of these TF motifs at IFN-EC signature genes. Expression of immune regulatory ligand genes by IFN-ECs suggests bidirectional signaling between IFN-ECs and macrophages in regenerative-stage hearts. Our data suggest that ECs may adopt immune regulatory signatures after cardiac injury to accompany the reparative response. The presence of these signatures in human HF and murine MI models suggests a potential role for EC-mediated immune regulation in responding to stress induced by acute injury in MI and chronic adverse remodeling in HF.
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Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Cardiology Commons, Cardiovascular Diseases Commons, Integrative Medicine Commons, Medical Sciences Commons
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