Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling

AbstractSystemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysi...

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Autores principales:	Rusan Catar, Guido Moll, Julian Kamhieh-Milz, Christian Luecht, Lei Chen, Hongfan Zhao, Lucas Ernst, Kevin Willy, Matthias Girndt, Roman Fiedler, Janusz Witowski, Henning Morawietz, Olle Ringdén, Duska Dragun, Kai-Uwe Eckardt, Ralf Schindler, Daniel Zickler
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cardiovascular disease endothelial cell (dys)function expanded hemodialysis therapy chronic kidney disease end-stage renal disease uremic toxins / systemic microinflammation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2b5da9f8659e4b1c889dc9aee829ea9d
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spelling	oai:doaj.org-article:2b5da9f8659e4b1c889dc9aee829ea9d2021-11-11T10:23:34ZExpanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling1664-322410.3389/fimmu.2021.774052https://doaj.org/article/2b5da9f8659e4b1c889dc9aee829ea9d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.774052/fullhttps://doaj.org/toc/1664-3224AbstractSystemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysis filters might offer improvements. We here studied the impact of novel improved molecular cut-off hemodialysis filters on systemic microinflammation, uremia and endothelial dysfunction. Human endothelial cells (ECs) were incubated with uremic serum obtained from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation (PERCI-II) crossover clinical trial, comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes, and then assessed for their vascular endothelial growth factor (VEGF) production and angiogenesis. Compared to HF membranes, dialysis with MCO membranes lead to a reduction in proinflammatory mediators and reduced endothelial VEGF production and angiogenesis. Cytokine multiplex screening identified tumor necrosis factor (TNF) superfamily members as promising targets. The influence of TNF-α and its soluble receptors (sTNF-R1 and sTNF-R2) on endothelial VEGF promoter activation, protein release, and the involved signaling pathways was analyzed, revealing that this detrimental signaling was indeed induced by TNF-α and mediated by AP-1/c-FOS signaling. In conclusion, uremic toxins, in particular TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel MCO membranes.Translational Perspective and Graphical AbstractSystemic microinflammation, altered cytokine signaling, cardiovascular disease, and endothelial maladaptation/dysfunction are common clinical complications in dialysis patients suffering from end-stage renal disease. We studied the impact of novel improved medium-cut-off hemodialysis filters on uremia and endothelial dysfunction. We can show that uremic toxins, especially TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel improved medium-cut-off membranes.Rusan CatarGuido MollGuido MollGuido MollJulian Kamhieh-MilzChristian LuechtLei ChenHongfan ZhaoLucas ErnstKevin WillyKevin WillyMatthias GirndtRoman FiedlerJanusz WitowskiHenning MorawietzOlle RingdénDuska DragunKai-Uwe EckardtRalf SchindlerDaniel ZicklerFrontiers Media S.A.articlecardiovascular diseaseendothelial cell (dys)functionexpanded hemodialysis therapychronic kidney diseaseend-stage renal diseaseuremic toxins / systemic microinflammationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiovascular disease endothelial cell (dys)function expanded hemodialysis therapy chronic kidney disease end-stage renal disease uremic toxins / systemic microinflammation Immunologic diseases. Allergy RC581-607
spellingShingle	cardiovascular disease endothelial cell (dys)function expanded hemodialysis therapy chronic kidney disease end-stage renal disease uremic toxins / systemic microinflammation Immunologic diseases. Allergy RC581-607 Rusan Catar Guido Moll Guido Moll Guido Moll Julian Kamhieh-Milz Christian Luecht Lei Chen Hongfan Zhao Lucas Ernst Kevin Willy Kevin Willy Matthias Girndt Roman Fiedler Janusz Witowski Henning Morawietz Olle Ringdén Duska Dragun Kai-Uwe Eckardt Ralf Schindler Daniel Zickler Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
description	AbstractSystemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysis filters might offer improvements. We here studied the impact of novel improved molecular cut-off hemodialysis filters on systemic microinflammation, uremia and endothelial dysfunction. Human endothelial cells (ECs) were incubated with uremic serum obtained from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation (PERCI-II) crossover clinical trial, comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes, and then assessed for their vascular endothelial growth factor (VEGF) production and angiogenesis. Compared to HF membranes, dialysis with MCO membranes lead to a reduction in proinflammatory mediators and reduced endothelial VEGF production and angiogenesis. Cytokine multiplex screening identified tumor necrosis factor (TNF) superfamily members as promising targets. The influence of TNF-α and its soluble receptors (sTNF-R1 and sTNF-R2) on endothelial VEGF promoter activation, protein release, and the involved signaling pathways was analyzed, revealing that this detrimental signaling was indeed induced by TNF-α and mediated by AP-1/c-FOS signaling. In conclusion, uremic toxins, in particular TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel MCO membranes.Translational Perspective and Graphical AbstractSystemic microinflammation, altered cytokine signaling, cardiovascular disease, and endothelial maladaptation/dysfunction are common clinical complications in dialysis patients suffering from end-stage renal disease. We studied the impact of novel improved medium-cut-off hemodialysis filters on uremia and endothelial dysfunction. We can show that uremic toxins, especially TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel improved medium-cut-off membranes.
format	article
author	Rusan Catar Guido Moll Guido Moll Guido Moll Julian Kamhieh-Milz Christian Luecht Lei Chen Hongfan Zhao Lucas Ernst Kevin Willy Kevin Willy Matthias Girndt Roman Fiedler Janusz Witowski Henning Morawietz Olle Ringdén Duska Dragun Kai-Uwe Eckardt Ralf Schindler Daniel Zickler
author_facet	Rusan Catar Guido Moll Guido Moll Guido Moll Julian Kamhieh-Milz Christian Luecht Lei Chen Hongfan Zhao Lucas Ernst Kevin Willy Kevin Willy Matthias Girndt Roman Fiedler Janusz Witowski Henning Morawietz Olle Ringdén Duska Dragun Kai-Uwe Eckardt Ralf Schindler Daniel Zickler
author_sort	Rusan Catar
title	Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
title_short	Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
title_full	Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
title_fullStr	Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
title_full_unstemmed	Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling
title_sort	expanded hemodialysis therapy ameliorates uremia-induced systemic microinflammation and endothelial dysfunction by modulating vegf, tnf-α and ap-1 signaling
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2b5da9f8659e4b1c889dc9aee829ea9d
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Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling

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