Journal
EUROPEAN HEART JOURNAL
Volume 36, Issue 29, Pages 1923-1934Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehv195
Keywords
Acute myocardial infarction; Monocytes; Genomics; Inflammation; Mitosis
Categories
Funding
- Wellcome Trust
- British Heart Foundation
- National Institutes of Health (NIH)
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
- British Heart Foundation [RG/13/8/30266, PG/12/46/29673, FS/13/71/30378] Funding Source: researchfish
- Medical Research Council [MR/K00266X/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10166] Funding Source: researchfish
- MRC [MR/K00266X/1] Funding Source: UKRI
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Aims Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans. The aim of this study was to investigate whether the monocyte response following AMI is conserved between humans and mice and interrogate patterns of gene expression to identify regulated functions. Methods and results Thirty patients (AMI) and 24 control patients (stable coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group) underwent AMI by surgical coronary ligation. Myocardial injury was quantified by magnetic resonance imaging (human) and echocardiography (mice). Peripheral monocytes were isolated at presentation and at 48 h. RNA from separated monocytes was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a significant peripheral monocytosis in both species that positively correlated with the extent of myocardial injury. Analysis of the monocyte transcriptome following AMI demonstrated significant conservation and identified inflammation and mitosis as central processes to this response. These findings were validated in both species. Conclusions Our findings show that the monocyte transcriptome is conserved between mice and humans following AMI. Patterns of gene expression associated with inflammation and proliferation appear to be switched on prior to their infiltration of injured myocardium suggesting that the specific targeting of inflammatory and proliferative processes in these immune cells in humans are possible therapeutic strategies. Importantly, they could be effective in the hours after AMI.
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