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The relationships among monocyte subsets,miRNAs and inflammatory cytokines in patients with acute myocardial infarction
Authors:Ewelina Kazimierczyk  Andrzej Eljaszewicz  Paula Zembko  Ewa Tarasiuk  Malgorzata Rusak  Agnieszka Kulczynska-Przybik  Marta Lukaszewicz-Zajac  Karol Kaminski  Barbara Mroczko  Maciej Szmitkowski  Milena Dabrowska  Bozena Sobkowicz  Marcin Moniuszko  Agnieszka Tycinska
Institution:1. Department of Cardiology, Medical University of Bialystok, Bia?ystok, Poland;2. Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bia?ystok, Poland;3. Department of Hematological Diagnostics, Medical University of Bialystok, Bia?ystok, Poland;4. Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Bia?ystok, Poland;5. Department of Biochemical Diagnostics, Medical University of Bialystok, Bia?ystok, Poland;6. Department of Population Medicine and Prevention of Civilization Diseases, Medical University of Bialystok, Bia?ystok, Poland;7. Department of Allergology and Internal Medicine, Medical University of Bialystok, Bia?ystok, Poland
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.
Keywords: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  Monocytes  Acute myocardial infarction-atherosclerosis  Cytokines  Cardiac remodeling
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