Circulatory mitochondrial DNA is a pro-inflammatory agent in maintenance hemodialysis patients.

Hongdi Cao,Weichun He,Xia Shen,Xiaochun Wu,Zongwei Song,Hong Ye,Junwei Yang,Chunsun Dai,Zhiping Sun,Emmanuel A. Burdmann

doi:10.1371/journal.pone.0113179

Hongdi Cao, Weichun He + Show 8 more

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https://doi.org/10.1371/journal.pone.0113179

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Journal: PloS one	Publication Date: Dec 8, 2014
Citations: 55	License type: CC BY 4.0

Affiliation: Nanjing Medical University

Abstract

Chronic inflammation is highly prevalent in maintenance hemodialysis (MHD) patients, and it has been shown to be a strong predictor of morbidity and mortality. Mitochondrial DNA (mtDNA) released into circulation after cell damage can promote inflammation in patients and animal models. However, the role and mechanisms of circulatory mtDNA in chronic inflammation in MHD patients remain unknown. Sixty MHD patients and 20 health controls were enrolled in this study. The circulatory mtDNA was detected by quantitative real-time PCR assay. Plasma interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were quantitated by ELISA assay. Dialysis systems in MHD patients and in vitro were used to evaluate the effect of different dialysis patterns on circulatory mtDNA. Circulatory mtDNA was elevated in MHD patients comparing to that of health control. Regression analysis demonstrated that plasma mtDNA was positively associated with TNF-α and the product of serum calcium and phosphorus, while negatively associated with hemoglobin and serum albumin in MHD patients. MtDNA induced the secretion of IL-6 and TNF-α in the THP-1 cells. Single high-flux hemodialysis (HF-HD) and on line hemodiafiltration (OL-HDF) but not low-flux hemodialysis (LF-HD) could partially reduce plasma mtDNA in MHD patients. In vitro, both HD and hemofiltration (HF) could fractional remove mtDNA. Collectively, circulatory mtDNA is elevated and its level is closely correlated with chronic inflammation in MHD patients. HF-HD and HDF can partially reduce circulatory mtDNA in MHD patients.

Highlights

Chronic inflammation is one of the characteristics of maintenance hemodialysis (MHD) patients, which has been shown to be a strong predictor of morbidity and mortality in this population [1]
MtDNA escaped from autophagy in the cardiomyocytes by external hemodynamic stress could lead to Toll Like Receptor (TLR)-9 mediated inflammatory responses and is capable of inducing myocarditis [11]
Chronic inflammation is highly prevalent in MHD patients, which is a strong independent predictor of allcause and cardiovascular disease (CVD) mortality in those population [1] [22] [23]

Summary

Introduction

Chronic inflammation is one of the characteristics of maintenance hemodialysis (MHD) patients, which has been shown to be a strong predictor of morbidity and mortality in this population [1]. It was demonstrated that chronic inflammation played an important role in the pathogenesis of cardiovascular disease (CVD) in MHD patients [2]. The increased levels of specific cytokines (interleukin 6 and tumor necrosis factor a) or acute phase proteins (C-reactive protein) have been found to be associated with CVD in MHD patients [3, 4]. It has been described that apoptotic cf-DNA was increased in the plasma of MHD patients, which selectively stimulated the production of proinflammatory cytokines from human monocyte [14]. The change of circulatory mtDNA in MHD patients and the mechanism in the formation of inflammatory state has not yet be concerned

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