Ruparelia, N, Godec, J, Lee, R et al. (13 more authors) (2015) Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans. European Heart Journal, 36 (29). pp. 1923-1934. ISSN 0195-668X
Abstract
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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | (c) The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Acute myocardial infarction; Monocytes; Genomics; Inflammation; Mitosis |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Biomedical Imaging Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Aug 2019 14:08 |
Last Modified: | 07 Aug 2019 14:08 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/eurheartj/ehv195 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:149006 |