M2 Monocyte Polarization in Dialyzed Patients Is Associated with Increased Levels of M-CSF and Myeloperoxidase-Associated Oxidative Stress: Preliminary Results

Valérie Pireaux,Pierre Van Antwerpen,Jean-Marc Desmet,Karim Zouaoui Boudjeltia,Cédric Delporte,Martine Raes,Alexandre Rousseau

doi:10.3390/biomedicines9010084

Valérie Pireaux, Pierre Van Antwerpen + Show 5 more

Open Access

https://doi.org/10.3390/biomedicines9010084

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Abstract

Cardiovascular diseases represent a major issue in terms of morbidity and mortality for dialysis patients. This morbidity is due to the accelerated atherosclerosis observed in these patients. Atherosclerosis is a chronic inflammatory disease characterized by key players such as monocytes, macrophages, or oxidized LDLs. Monocytes-macrophages are classified into subsets of polarized cells, with M1 and M2 macrophages considered, respectively, as pro- and anti-inflammatory. (1) Methods: The monocyte subsets and phenotypes were analyzed by flow cytometry. These data were completed by the quantification of plasma M-CSF, IL-8, CRP, Mox-LDLs, Apo-B, Apo-AI, chloro-tyrosine, and homocitrulline concentrations. The statistical differences and associations between two continuous variables were assessed using the Mann–Whitney U test and Spearman’s correlation coefficient, respectively. (2) Results: Hemodialyzed patients showed a significant increase in their concentrations of CRP, M-CSF, and IL-8 (inflammation biomarkers), as well as chloro-tyrosine and homocitrulline (myeloperoxidase-associated oxidative stress biomarkers). Moreover, we observed a higher percentage of M2 monocytes in the plasma of hemodialysis patients as compared to the controls. (3) Conclusions: Our data suggest that oxidative stress and an inflammatory environment, which is amplified in hemodialysis patients, seems to favor an increase in the concentration of circulating M-CSF, therefore leading to an increase in M2 polarization among circulating monocytes.

Highlights

The morbidity associated with Cardiovascular diseases (CVD) is due to accelerated atherosclerosis, which has been shown to be present in the carotid arteries of HD patients as opposed to aged-matched healthy controls, with a higher thickness of the media/intima as well as with arterial stiffness and calcification within the plaques [3,4,5,6]
This oxidation activates endothelial cells, enhancing chemokine and cytokine secretion and inducing the recruitment of monocytes that will differentiate into macrophages in the intima [8,9]
We investigated whether the polarization of circulating monocytes would be different in hemodialysis patients versus healthy volunteers and whether it could be correlated with the inflammatory status, as assessed by quantifying inflammatory proteins (IL-8, CRP, and macrophage-colony stimulating factor (M-CSF)) in the plasma

Summary

Introduction

Cardiovascular diseases (CVD) account for approximately 30% to 40% of deaths among dialysis patients ([1], updated 19 September 2016). They represent a major issue in terms of morbidity and mortality for the latter, and in the case of hemodialyzed (HD) patients showing a 5-year survival rate on stable HD (for a review, see [2]). Injuries or local blood flow perturbations lead to increased permeability of the endothelial layer, favoring lipoprotein infiltration in the intima where they are oxidized and become atherogenic (for reviews, see [7,8,9]). This oxidation activates endothelial cells, enhancing chemokine and cytokine secretion and inducing the recruitment of monocytes that will differentiate into macrophages in the intima [8,9]

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