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.

Eur Heart J

Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DU, UK Oxford Heart Centre, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK Acute Vascular Imaging Centre, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford OX3 9DU, UK

Published: August 2015

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571177PMC
http://dx.doi.org/10.1093/eurheartj/ehv195DOI Listing

Publication Analysis

Top Keywords

acute myocardial
12
myocardial infarction
12
inflammation proliferation
8
mice humans
8
monocytes play
8
targeting inflammatory
8
patterns gene
8
gene expression
8
myocardial injury
8
monocyte transcriptome
8

Similar Publications

[Management of acute coronary syndrome].

Herz

January 2025

Herzzentrum Leipzig, Universitätsklinik für Kardiologie, Strümpellstr. 39, 04289, Leipzig, Deutschland.

Coronary artery disease (CAD) is the leading cause of death worldwide. Acute coronary syndrome (ACS) encompasses a spectrum of diagnoses ranging from unstable angina pectoris to myocardial infarction with and without ST-segment elevation and frequently presents as the first clinical manifestation. It is crucial in this scenario to perform a timely and comprehensive assessment of patients by evaluating the clinical presentation, electrocardiogram and laboratory diagnostics using highly sensitivity cardiac troponin in order to initiate a timely and risk-adapted continuing treatment with immediate or early invasive coronary angiography.

View Article and Find Full Text PDF

Cardiogenic shock represents a critical condition in which the heart is unable to maintain adequate circulation leading to insufficient tissue perfusion and end-organ failure. Temporary mechanical circulatory support offers the potential to stabilize patients, provide a bridge-to-recovery, provide a bridge-to-decision, or facilitate definitive heart replacement therapies. Although randomized controlled trials have been performed in infarct-related cardiogenic shock and refractory cardiac arrest, the optimal timing, appropriate patient selection, and optimal implementation of these devices remain complex and predominantly based on observational data and expert consensus, especially in non-ischaemic shock.

View Article and Find Full Text PDF

Introduction: Despite its low prevalence, premature myocardial infarction (MI) bears serious social consequences and shares different pathophysiology.

Objectives: The aim of the study was to evaluate young MI patients in terms of clinical characteristics and long-term outcomes.

Patients And Methods: This study is an observational research covering 221 patients <45 years old [16.

View Article and Find Full Text PDF

Background: Excessive supraventricular ectopic activity (ESVEA) is regarded as a risk marker for later atrial fibrillation (AF) detection.

Methods And Results: The investigator-initiated, prospective, open, multicenter MonDAFIS (Impact of Standardized Monitoring for Detection of Atrial Fibrillation in Ischemic Stroke) study randomized 3465 patients with acute ischemic stroke without known AF 1:1 to usual diagnostic procedures for AF detection or additive Holter monitoring in hospital for up to 7 days, analyzed in a core laboratory. Secondary study objectives include the comparison of recurrent stroke, myocardial infarction, major bleeding, and all-cause death within 24 months in patients with ESVEA (defined as ectopic supraventricular beats ≥480/day or atrial runs of 10-29 seconds or both) versus patients with newly diagnosed AF versus patients without ESVEA or AF (non-ESVEA/AF), randomized to the intervention group.

View Article and Find Full Text PDF

Background: Meta-analyses have suggested that the risk of cardiovascular disease events is significantly higher after a chronic obstructive pulmonary disease (COPD) exacerbation, but the populations at highest risk have not been well characterized to date.

Methods And Results: The authors analyzed the risk of atherosclerotic cardiovascular disease (ASCVD) hospitalizations after COPD hospitalization compared with before COPD hospitalization and patient factors associated with ASCVD hospitalizations after COPD hospitalization among 2 high-risk patient cohorts. The primary outcome was risk of an ASCVD hospitalization composite outcome (myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, stroke, transient ischemic accident) after COPD hospitalization relative to before COPD hospitalization.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!