Abstract
Background
Acute myocardial infarction (AMI) causes irreversible myocardial damage and release of inflammatory mediators, including cytokines, chemokines and miRNAs. We aimed to investigate changes in the levels of cytokines (IL-6, TNF-α and IL-10), miRNAs profiles (miR-146 and miR-155) and distribution of different monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) in the acute and post-healing phases of AMI.
Methods
In eighteen consecutive AMI patients (mean age 56.78 ± 12.4 years, mean left ventricle ejection fraction — LVEF: 41.9 ± 9.8%), treated invasively, monocyte subsets frequencies were evaluated (flow cytometry), cytokine concentrations were analyzed (ELISA) as well as plasma miRNAs were isolated twice — on admission and after 19.2 ± 5.9 weeks of follow-up. Measurements were also performed among healthy volunteers.
Results
AMI patients presented significantly decreased frequencies of classical cells in comparison to healthy controls (median 71.22% [IQR: 64.4–79.04] vs. 84.35% [IQR: 81.2–86.7], p = 0.001) and higher percent of both intermediate and non-classical cells, yet without statistical significance (median 6.54% [IQR: 5.14–16.64] vs. 5.87% [IQR: 4.48–8.6], p = 0.37 and median 5.99% [IQR: 3.39–11.5] vs. 5.26% [IQR: 3.62–6.2], p = 0.42, respectively). In AMI patients both, analyzed plasma miRNA concentrations were higher than in healthy subjects (miR-146: median 5.48 [IQR: 2.4–11.27] vs. 1.84 [IQR: 0.87–2.53], p = 0.003; miR-155: median 25.35 [IQR: 8.17–43.15] vs. 8.4 [IQR: 0.08–16.9], p = 0.027, respectively), and returned back to the values found in the control group in follow-up. miR-155/miR-146 ratio correlated with the frequencies of classical monocytes (r=0.6, p = 0.01) and miR-155 correlated positively with the concentration of inflammatory cytokines − IL-6 and TNF-α.
Conclusions
These results may suggest cooperation of both pro-inflammatory and anti-inflammatory signals in AMI in order to promote appropriate healing of the infarcted myocardium.
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Abbreviations
- AMI:
-
acute myocardial infarction
- CAD:
-
coronary artery disease
- CCL2:
-
chemokine (C-C motif) ligand 2
- CCR2:
-
C-C chemokine receptor type 2
- ESC:
-
European Society of Cardiology
- HSC:
-
hematopoietic stem cell
- IL:
-
interleukin
- Inpp5d:
-
Inositol Polyphosphate-5-Phosphatase D
- IRAK1:
-
interleukin-1 receptor-associated kinase 1
- LVEF:
-
left ventricle ejection fraction
- LPS:
-
lipopolysaccharide
- miRNA:
-
micro RNA
- pPCI:
-
primary percutaneous coronary intervention
- ROS:
-
reactive oxygen species
- Socs1:
-
Suppressor of cytokine signaling 1
- TNF-α:
-
tumour necrosis factor α
- TRAF6:
-
TNF receptor associated factor 6
- WMSI:
-
wall-motion score index
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Kazimierczyk, E., Eljaszewicz, A., Zembko, P. et al. The relationships among monocyte subsets, miRNAs and inflammatory cytokines in patients with acute myocardial infarction. Pharmacol. Rep 71, 73–81 (2019). https://doi.org/10.1016/j.pharep.2018.09.007
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DOI: https://doi.org/10.1016/j.pharep.2018.09.007