Hemodialysis Removes Uremic Toxins That Alter the Biological Actions of Endothelial Cells

Zafeiropoulou, Kalliopi; Bita, Theodora; Polykratis, Apostolos; Karabina, Stella; Vlachojannis, John G.; Katsoris, Panagiotis

doi:10.1371/journal.pone.0030975

Cited by 22 publications

(24 citation statements)

References 68 publications

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“…In our previous study, we found that serum obtained at the end of the hemodialysis session stimulated the proliferation of endothelial cells and synthesis of MCP-1 in these cells [6]. Similar observations were presented by Zafeiropoulou et al [7]. These effects could be due to the removal of uremic toxins during dialysis which makes serum less harmful to the endothelial cells but at the same time dialysis-induced inflammatory reaction may stimulate these cells [6,7].…”

Section: Introductionsupporting

confidence: 77%

“…Similar observations were presented by Zafeiropoulou et al [7]. These effects could be due to the removal of uremic toxins during dialysis which makes serum less harmful to the endothelial cells but at the same time dialysis-induced inflammatory reaction may stimulate these cells [6,7]. All studies were performed on human umbilical venous endothelial cells (VECs).…”

Section: Introductionsupporting

confidence: 65%

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Different Effect of Hemodialysis on Function of Human Arterial and Venous Endothelial Cells

et al. 2018

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Background/aims: Hemodialysis causes the systemic inflammatory response, which may affect the function of endothelial cells. Methods: We studied the effect of the serum obtained after a hemodialysis session, compared to serum collected before the start of the treatment, on the gene expression and secretory activity of arterial endothelial cells (AECs) and venous endothelial cells (VECs) in in vitro culture. Results: Serum collected at the end of the hemodialysis session increased expression of the studied genes in VECs, and at the same time decreased their expression in AECs. Secretory activity was increased in VEC: (interleukin-6 [IL-6] +29%, p < 0.05, von Willebrand factor +23%, p < 0.02; tissue plasminogen activator [t-PA] +35%, p < 0.002, t-PA/plasminogen activator inhibitor-1 [PAI-1] ratio + 57%, p < 0.005). In AEC, synthesis of IL-6 and vascular endothelial growth factor were reduced (–36%, p < 0.02, –34%, p < 0.05, respectively) and the tPA/PAI-1 ratio was increased (+22%, p < 0.01). Conclusions: Hemodialysis induces the inflammatory, procoagulant, and profibrinolytic activity of VEC, whereas suppression of AEC is observed at the same time. Video Journal Club ‘Cappuccino with Claudio Ronco’ at https://www.karger.com/Journal/ArticleNews/223997?sponsor=52

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Section: Introductionsupporting

confidence: 77%

Section: Introductionsupporting

confidence: 65%

Different Effect of Hemodialysis on Function of Human Arterial and Venous Endothelial Cells

et al. 2018

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“…Other reports provided similar information by comparing endothelial cell toxicity of uraemic serum derived from patients before or after haemodialysis (Zafeiropoulou et al . ). Furthermore, we observed an increased ROS production, as previously reported (Carracedo et al .…”

Section: Discussionmentioning

confidence: 97%

Effect of uraemia on endothelial cell damage is mediated by the integrin linked kinase pathway

García-Jérez

Luengo

Carracedo

et al. 2014

The Journal of Physiology

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Key pointsr Patients with chronic kidney disease have a higher risk of developing cardiovascular diseases than the general population. Their vascular endothelium is dysfunctional, among other things, because it is permanently exposed to uraemic toxins, several of which have poor clearance by conventional dialysis.r Recent studies have demonstrated the important role of integrin-linked kinase (ILK) in the maintenance of endothelial integrity and in this study we investigate the involvement of ILK in the mechanism underlying vascular endothelial damage that occurs in uraemia.r For the first time, we demonstrate the implication of ILK in the protection against endothelial cell damage (inhibition of proliferation, toxicity, oxidative stress and programed cell death) induced by uraemic serum from chronic kidney disease patients and uraemic toxins.r This molecular mechanism may have clinical relevance because it highlights the importance of maintaining high levels of ILK activity to help preserve endothelial integrity, at least in early stages of chronic kidney disease.Abstract Patients with chronic kidney disease (CKD) have a higher risk of developing cardiovascular diseases. Their vascular endothelium is dysfunctional, among other things, because it is permanently exposed to uraemic toxins, several of which, mostly protein-bound compounds such as indoxyl sulfate (IS) and p-cresyl sulphate, having poor clearance by conventional dialysis, induce endothelial toxicity. However, the molecular mechanism by which uraemic toxins regulate early stages of endothelial dysfunction remains unclear. Recent studies have demonstrated the important role of integrin-linked kinase (ILK) in the maintenance of endothelial integrity. In this study, we investigate the involvement of ILK in the mechanism underlying vascular endothelial damage that occurs in uraemia. First, we show that incubation of EA.hy926 cells with human uraemic serum from CKD patients upregulates ILK activity. This ILK activation also occurs when the cells are exposed to IS (25-100 μg ml −1 ), p-cresol (10-100 μg ml −1 ) or both combined, compared to human serum control. Next, we observed that high doses of both toxins together induce a slight decrease in cell proliferation and increase apoptosis and reactive oxygen species production. Interestingly, these toxic effects displayed a strong increase when the ILK protein is knocked down by small interfering RNA, even at low doses of uraemic toxins. Abrogation of AKT has demonstrated the ILK/AKT signalling pathway involved in these processes. This study has demonstrated the implication of ILK in the protection against endothelial cell damage induced by uraemic toxins, a molecular mechanism that could play a protective role in the early stages of endothelial dysfunction observed in uraemic patients.

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“…Additionally, MMP-9 is also produced and secreted by several cell types, including vascular endothelial cells. HD removing uremic toxins can decrease MMP-9 expression of vascular endothelial cells [39]. Overall the discussion above, insignificant difference of plasma MMP-9 activity between pre-HD and post-HD detected could be reasonably explained.…”

Section: Discussionmentioning

confidence: 62%

“…Increased circulating MMPs production and/or MMPs/TIMPs ratio seem to correlate more with increased thrombotic incidence and atherosclerosis observed in the patients with CKD [4,5]. Zafeiropoulou et al [39] have demonstrated that removal of circulating uremic toxins by HD treatment could reduce the MMPs (MMP-2 and MMP-9) and enhance TIMPs (TIMP-1 and TIMP-2) production by vascular endothelial cells in vitro as well as their enzymatic activity. This proposition is confirmed by Rysz et al [20], they indicated that route HD-related washout of uremic toxins would partially explain the decrease of MMP-2 in the patients.…”

Section: Discussionmentioning

confidence: 99%

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

Yang

Hsieh

et al. 2015

Clin Exp Nephrol

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Background Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) play important roles in the pathophysiology of renal diseases. Imbalanced MMPs/TIMPs are implicated in the vascular alterations of uremic patients on hemodialysis (HD). We have investigated the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in uremic patients and the effects of a course of HD on the changes in these factors. Methods There were 382 uremic patients on regular HD treatment and 50 healthy controls enrolled in this study. The plasma MMP-2 and MMP-9 levels were detected by gelatin zymography, and TIMP-1 and TIMP-2 concentrations were determined by ELISA assay. Results Significantly higher plasma MMP-2 and MMP-9 and decreased TIMP-1 in the uremic patients were detected compared with those in the controls. Therefore, there were markedly higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in the uremic patients. In the course of a single HD session, the plasma MMP-2 level was significantly decreased from pre-HD to post-HD. TIMP-1 concentration was significantly increased from pre-HD to post-HD. Although the HD session did not have a significant effect on the levels of plasma MMP-9 and TIMP-2, both plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios were significantly decreased from pre-HD to post-HD levels.Conclusion HD session could decrease MMP-2 and increase TIMP-1 level in the circulation of uremic patients. The physiological significance of reduced MMPs/TIMPs ratio due to a single HD session is required to further validate.Keywords Hemodialysis Á Matrix metalloproteinase Á Tissue inhibitor of matrix metalloproteinase Á Uremic patient

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Hemodialysis Removes Uremic Toxins That Alter the Biological Actions of Endothelial Cells

Cited by 22 publications

References 68 publications

Different Effect of Hemodialysis on Function of Human Arterial and Venous Endothelial Cells

Different Effect of Hemodialysis on Function of Human Arterial and Venous Endothelial Cells

Effect of uraemia on endothelial cell damage is mediated by the integrin linked kinase pathway

Decreases in plasma MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in uremic patients during hemodialysis

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