Uremic serum inhibits<i>in vitro</i>expression of chemokine SDF-1: impact of uremic toxicity on endothelial injury

Ribeiro, Vanessa Bley; Bosquetti, Bruna; Gonçalves, Simone; Bucharles, Sérgio Gardano Elias; Rempel, Lisienny Campoli Tono; Maciel, Rayana Ariane Pereira; Oliveira, Rodrigo Bueno de; Pécoits-Filho, Roberto; Stinghen, Andréa Emília Marques

doi:10.5935/0101-2800.20140021

Cited by 10 publications

(8 citation statements)

References 41 publications

(46 reference statements)

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“…Exposure of the endothelium to uremic toxins leads to a series of changes in vascular homeostasis and its functions [39]. We demonstrated previously—using this same model—that uremic plasma activates inflammatory pathways by inducing the production of chemokines and adhesion molecules, usually present in early events of atherosclerosis in CKD patients [14, 40]. We also observed, using endothelial cells and monocytes treated with AGEs, that both cells were activated by AGEs via RAGE through protein kinase C beta pathway, producing MCP-1 and VCAM-1 [27].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have implicated a causal role of SAA as a pro-inflammatory and pro-thrombotic mediator in the pathogenesis of atherosclerosis [43]. Moreover, others have shown that SAA is a potent pro-atherogenic chemokine on the endothelium, inducing the expression of cytokines and adhesion molecules such as IL-6, IL-8, MCP-1, ICAM-1, VCAM-1 and tissue factor [40, 44, 45]. Furthermore, AGEs increase the endothelial cell levels of mRNA coding for PAI-1 mediated by RAGE [46].…”

Section: Discussionmentioning

confidence: 99%

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Sevelamer reduces endothelial inflammatory response to advanced glycation end products

Gregório

Favretto

Sassaki

et al. 2017

Clinical Kidney Journal

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BackgroundAdvanced glycation end products (AGEs) have been related to the pathogenesis of cardiovascular diseases (CVD), chronic kidney disease (CKD) and diabetes mellitus. We sought to investigate the binding capacity of sevelamer to both AGEs and uremic serum in vitro and then test this pharmaceutical effect as a potential vascular anti-inflammatory strategy.MethodsAGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. Human endothelial cells were incubated in culture media containing AGEs and uremic serum with or without sevelamer. Receptor for advanced glycation end product (RAGE) expression was evaluated through immunocytochemistry and western blot to explore the interactions between AGEs and the endothelium. Inflammatory and endothelial dysfunction biomarkers, such as interleukin 6 (IL-6) and IL-8, monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and serum amyloid A (SAA) were also measured in cell supernatant. The chemotactic property of the supernatant was evaluated. ResultsAGEs significantly induced the expression of RAGE, inflammatory and endothelial activation biomarkers [IL-6, (P < 0.005); IL-8, MCP-1, PAI-1 and SAA (P < 0.001)] and monocyte chemotaxis as compared with controls. In addition, AGEs increased the levels of inflammatory biomarkers, which were observed after 6 h of endothelial cell incubation with uremic serum [IL-6 (P < 0.001) IL-8, MCP-1 and PAI-1 (P < 0.05)]. On the other hand, after 6 h of endothelial cell treatment with sevelamer, RAGE expression (P < 0.05) and levels of inflammatory biomarkers [IL-6 and IL-8 (P < 0.001), MCP-1 (P < 0.01), PAI-1 and SAA (P < 0.005)] significantly decreased compared with the AGEs/uremic serum treatment alone.ConclusionsSevelamer decreased both endothelial expression of RAGE and endothelial dysfunction biomarkers, induced by AGEs, and uremic serum. Further studies are necessary for a better understanding of the potential protective role of sevelamer on uremic serum and AGEs-mediated endothelial dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sevelamer reduces endothelial inflammatory response to advanced glycation end products

Gregório

Favretto

Sassaki

et al. 2017

Clinical Kidney Journal

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“…We also demonstrated the presence of elevated levels of MCP-1 in uremic plasma, especially in patients with advanced stage of CKD [ 29 ]. VEGF and SDF-1 attract endothelial progenitor cells (EPCs) from the bone marrow to the injury site, leading to the activation of endothelial cells [ 22 , 25 , 26 , 30 ]. Ribeiro et al [ 30 ] showed that uremic serum can decrease the levels of SDF-1 in human umbilical vein endothelial cells (HUVECs) in comparison with healthy serum after 6 h, while IL-8 concentration increased within 12 h, indicating a poor vascular adaptation of patients with CKD [ 31 , 32 ].…”

Section: Endothelial Dysfunction In Ckdmentioning

confidence: 99%

How do Uremic Toxins Affect the Endothelium?

Cunha

Santos

Barreto

et al. 2020

Toxins

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Uremic toxins can induce endothelial dysfunction in patients with chronic kidney disease (CKD). Indeed, the structure of the endothelial monolayer is damaged in CKD, and studies have shown that the uremic toxins contribute to the loss of cell–cell junctions, increasing permeability. Membrane proteins, such as transporters and receptors, can mediate the interaction between uremic toxins and endothelial cells. In these cells, uremic toxins induce oxidative stress and activation of signaling pathways, including the aryl hydrocarbon receptor (AhR), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The activation of these pathways leads to overexpression of proinflammatory (e.g., monocyte chemoattractant protein-1, E-selectin) and prothrombotic (e.g., tissue factor) proteins. Uremic toxins also induce the formation of endothelial microparticles (EMPs), which can lead to the activation and dysfunction of other cells, and modulate the expression of microRNAs that have an important role in the regulation of cellular processes. The resulting endothelial dysfunction contributes to the pathogenesis of cardiovascular diseases, such as atherosclerosis and thrombotic events. Therefore, uremic toxins as well as the pathways they modulated may be potential targets for therapies in order to improve treatment for patients with CKD.

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“…In HD patients who developed ESRD as the result of chronic glomerulonephritis, hypertensive nephropathy or diabetic kidney disease, the serum levels of IL-8 and SDF-1 were increased when compared to healthy volunteers (Ribeiro et al, 2014). After an in vitro exposure of endothelial cells harvested from the HD patients to uremic toxins, the cellular expression of SDF-1 decreased, while the expression of IL-8 was increased (Ribeiro et al, 2014).…”

Section: Dialysismentioning

confidence: 99%

Endothelial progenitor cells participation in cardiovascular and kidney diseases: a systematic review

et al. 2016

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Endothelial progenitor cells (EPCs) represent a small population of blood cells (5-40 cells/mm(3)), with an ability to differentiate into endothelial cells that form the lining of the blood vessels and contribute to postnatal angiogenesis. Abundant evidence shows that recruitment of EPCs from the bone marrow, the monocyte/macrophage lineage and the organs facilitate the endothelial regeneration and repair. Changes in the number of EPCs were observed in both, chronic kidney and cardiovascular diseases. Thus, these cells were tested for usage in diagnosis and therapy. In this paper, we review the current knowledge on the EPC biology and contribution of these cells to the kidney and cardiovascular diseases.

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Uremic serum inhibitsin vitroexpression of chemokine SDF-1: impact of uremic toxicity on endothelial injury

Abstract: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia.

Cited by 10 publications

References 41 publications

Sevelamer reduces endothelial inflammatory response to advanced glycation end products

Sevelamer reduces endothelial inflammatory response to advanced glycation end products

How do Uremic Toxins Affect the Endothelium?

Endothelial progenitor cells participation in cardiovascular and kidney diseases: a systematic review

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