Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells

Lee, Chien-Te; Lee, Yueh‐Ting; Ng, Hwee-Yeong; Chiou, Terry Ting-Yu; Cheng, Cheng‐I; Kuo, Chung-Wen; Wu, Chien-Hsing; Chi, Po-Jui; Lee, Wen‐Chin

doi:10.1016/j.lfs.2011.10.014

Cited by 12 publications

(11 citation statements)

References 28 publications

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“…In monocytes, IS induces ROS production in an NADPH oxidase-dependent manner [98]. Furthermore, IS induces endothelial E-selectin [99], VCAM-1 [100], and ICAM-1 [100,101] expression. IS also induces the expression of MCP-1 [78,100,101,102], which is abolished by an AhR antagonist [78].…”

Section: Ahr-activating Uremic Toxins Induce Leukocyte Activation mentioning

confidence: 99%

“…Furthermore, IS induces endothelial E-selectin [99], VCAM-1 [100], and ICAM-1 [100,101] expression. IS also induces the expression of MCP-1 [78,100,101,102], which is abolished by an AhR antagonist [78]. MCP-1 induction by IS involves a ROS/MAPK/NF-κB pathway [101,102], which evokes the involvement of the inflammatory non-genomic pathway of AhR.…”

Section: Ahr-activating Uremic Toxins Induce Leukocyte Activation mentioning

confidence: 99%

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The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

Sallée

Dou

Cérini

et al. 2014

Toxins

214

178

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Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular diseases and suffer from accelerated atherosclerosis. CKD patients are permanently exposed to uremic toxins, making them good candidates as pathogenic agents. We focus here on uremic toxins from tryptophan metabolism because of their potential involvement in cardiovascular toxicity: indolic uremic toxins (indoxyl sulfate, indole-3 acetic acid, and indoxyl-β-d-glucuronide) and uremic toxins from the kynurenine pathway (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid). Uremic toxins derived from tryptophan are endogenous ligands of the transcription factor aryl hydrocarbon receptor (AhR). AhR, also known as the dioxin receptor, interacts with various regulatory and signaling proteins, including protein kinases and phosphatases, and Nuclear Factor-Kappa-B. AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and some polychlorinated biphenyls is associated with an increase in cardiovascular disease in humans and in mice. In addition, this AhR activation mediates cardiotoxicity, vascular inflammation, and a procoagulant and prooxidant phenotype of vascular cells. Uremic toxins derived from tryptophan have prooxidant, proinflammatory, procoagulant, and pro-apoptotic effects on cells involved in the cardiovascular system, and some of them are related with cardiovascular complications in CKD. We discuss here how the cardiovascular effects of these uremic toxins could be mediated by AhR activation, in a “dioxin-like” effect.

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Section: Ahr-activating Uremic Toxins Induce Leukocyte Activation mentioning

confidence: 99%

Section: Ahr-activating Uremic Toxins Induce Leukocyte Activation mentioning

confidence: 99%

The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

Sallée

Dou

Cérini

et al. 2014

Toxins

214

178

View full text Add to dashboard Cite

show abstract

“…Tissue factor is upregulated by oxidized low-density lipoprotein [30], asymmetric dimethylarginine [31], advanced glycation end products [32], and IS [17]. Statin reduced tissue factor production [33], but failed to improve IS-induced endothelial dysfunction [34]. The results of this study disclosed that Ang-(1-7) blocks IS-induced tissue factor expression.…”

Section: Discussionmentioning

confidence: 99%

Indoxyl Sulfate Downregulates Mas Receptor via Aryl Hydrocarbon Receptor/Nuclear Factor-kappa B, and Induces Cell Proliferation and Tissue Factor Expression in Vascular Smooth Muscle Cells

Wulaer

Lee

et al. 2016

Nephron

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Background/Aim: Angiotensin converting enzyme-related carboxypeptidase 2/angiotensin (Ang)-(1-7)/Mas receptor axis is protective in the development of chronic kidney disease and cardiovascular disease. This study is aimed at investigating whether indoxyl sulfate (IS) affects Mas receptor expression, cell proliferation and tissue factor expression in vascular smooth muscle cells, and if Ang-(1-7), an activator of Mas receptor, counteracts the IS-induced effects. Methods: IS was administered to normotensive and hypertensive rats. Human aortic smooth muscle cells (HASMCs) were cultured with IS. Results: IS reduced the expression of Mas receptor in the aorta of normotensive and hypertensive rats. IS downregulated the Mas receptor expression in a time- and dose-dependent manner in HASMCs. Knockdown of aryl hydrocarbon receptor (AhR) and nuclear factor-kappa B (NF-κB) inhibited IS-induced downregulation of Mas receptor. Further, IS stimulated cell proliferation and tissue factor expression in HASMCs. Ang-(1-7) attenuated IS-induced cell proliferation and tissue factor expression in HASMCs. Ang-(1-7) suppressed phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and NF-κB in HASMCs. Conclusion: IS downregulated the expression of Mas receptor via AhR/NF-κB, and induced cell proliferation and tissue factor expression in HASMCs. Ang-(1-7) inhibited IS-induced cell proliferation and tissue factor expression by suppressing the phosphorylation of ERK1/2 and NF-κB p65.

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“…Several agents have been shown to diminish or prevent indoxyl sulphate‐induced injury via various mechanisms . However, cardiovascular protective agents such as statins do not have any beneficial effects …”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone attenuates indoxyl sulphate‐induced endothelial dysfunction

Chou

Kuo

et al. 2015

Clin Exp Pharma Physio

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Indoxyl sulphate is a protein-bound uraemic toxin that has deleterious effects on the cardiovascular system. Rosiglitazone (RGZ) is an insulin sensitizer used for glycaemic control in type 2 diabetes. Rosiglitazone has been shown to be beneficial for cardiovascular disease because of its pleiotropic effects. Whether RGZ can improve indoxyl sulphate-induced endothelial damage has not been investigated. In the present in vitro study, we examined the effects of RGZ on indoxyl sulphate-induced endothelial injury. Endothelial cells were exposed to RGZ (5 and 10 μmol/L) and then treated with indoxyl sulphate (100 and 1000 μmol/L) for 48 h. Indoxyl sulphate upregulated intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 expression. Indoxyl sulphate also increased the abundance of NADPH oxidase 4 (NOX4) and nuclear factor (NF)-κB. Both extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) signalling pathways were activated after 48 h treatment with indoxyl sulphate. Pretreatment of cells with both concentrations of RGZ improved indices of endothelial injury. In addition, RGZ attenuated the increase in NOX4 and NF-κB and prevented the activation of the ERK1/2 and p38 MAPK signalling pathways. We conclude that RGZ ameliorates indoxyl sulphate-induced endothelial injury.

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Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells

Cited by 12 publications

References 28 publications

The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

Indoxyl Sulfate Downregulates Mas Receptor via Aryl Hydrocarbon Receptor/Nuclear Factor-kappa B, and Induces Cell Proliferation and Tissue Factor Expression in Vascular Smooth Muscle Cells

Rosiglitazone attenuates indoxyl sulphate‐induced endothelial dysfunction

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