Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells

Addi, Tawfik; Poitevin, Stéphane; McKay, Nathalie; Mecherfi, Kamel Eddine El; Khéroua, O.; Jourde-Chiche, Noémie; Macedo, Alix de; Gondouin, Bertrand; Cérini, Claire; Brunet, Philippe; Dignat-George, Françoise; Burtey, Stéphane; Dou, Laetitia

doi:10.1007/s00204-018-2328-3

Cited by 55 publications

(63 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3 We and others have demonstrated that TF, the main initiator of the coagulation, is increased in the plasma of patients with CKD 8,35 and that it is overexpressed in endothelial cells and vascular smooth muscle cells in response to various tryptophan-derived uremic toxin (TDUT) in vitro. 6,8,10,36 Here we show the TF increases in the aorta and in the wall of renal vessels in both types of CKD mice. In addition, we also observed renal expression of TF in arterioles and peritubular capillaries in adenine-fed mice highlighting the role of local inflammation in TF induction for this model.…”

Section: Discussionsupporting

confidence: 56%

“…These indolic compounds induce tissue factor (TF) in both the endothelial cells and vascular smooth muscle cells (vSMCs). 6,8,10,11 In CKD patients, the balance of pro-and antithrombotic factors in blood is altered. Indeed, several prothrombotic hemostatic mediators are elevated, including fibrinogen, soluble thrombomodulin, soluble TF, thrombin-antithrombin TAT complex, von Willebrand factor, Factor VIII, and C-reactive protein (CRP).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy

Makhloufi

Crescence

Darbousset

et al. 2020

TH Open

Self Cite

View full text Add to dashboard Cite

The coexistence of bleeding and thrombosis in patients with chronic kidney disease (CKD) is frequent and poorly understood. Mouse models are essential to understand complications of CKD and to develop new therapeutic approaches improving the health of patients. We evaluated the hemostasis in two models of renal insufficiency: adenine-diet and 5/6th nephrectomy (5/6Nx). Compared with 5/6Nx mice, mice fed with 0.25% adenine had more severe renal insufficiency and so higher levels of prothrombotic uremic toxins like indoxyl sulfate. More severe renal inflammation and fibrosis were observed in the adenine group, as demonstrated by histological and reverse transcription quantitative polymerase chain reaction experiments. Liver fibrinogen γ chain expression and level of plasma fibrinogen were increased only in adenine mice. In both CKD mouse models, tissue factor (TF) expression was increased in kidney and aorta extracts. Immunochemistry analysis of kidney sections showed that TF is localized in the vascular walls. Thrombin–antithrombin complexes were significantly increased in plasma from both adenine and 5/6Nx mice. Tail bleeding time increased significantly only in adenine mice, whereas platelet count was not significant altered. Finally, results obtained by intravital microscopy after laser-induced endothelial injury showed impaired platelet function in adenine mice and an increase in fibrin generation in 5/6Nx mice. To summarize, adenine diet causes a more severe renal insufficiency compared with 5/6Nx. The TF upregulation and the hypercoagulable state were observed in both CKD models. Bleeding tendency was observed only in the adenine model of CKD that recapitulates the whole spectrum of hemostasis abnormalities observed in advanced human CKD.

show abstract

Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy

Makhloufi

Crescence

Darbousset

et al. 2020

TH Open

Self Cite

View full text Add to dashboard Cite

show abstract

“…AhR protein expression was additionally positively associated with plasma levels of another indolic uremic toxin, indole-3 acetic acid (IAA) [88]. IAA is responsible for some adverse effects potentially related to the increased cardiovascular risk of CKD patients, such as increasing the expression of tissue factor in human vascular cells via the AhR [89]. However, up to now it is unknown to what extent the circadian expression of AhR is disrupted in CKD, what role might uremic toxins and the microbiota have in this phenomenon and what the consequences in any alterations in this system circadian regulation might be for CKD patients.…”

Section: Uremic Toxinsmentioning

confidence: 99%

Chronodisruption: A Poorly Recognized Feature of CKD

Carriazo

Ramos

Sanz

et al. 2020

Toxins

View full text Add to dashboard Cite

Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

show abstract

“…Açaí fruits from the Amazon region (Belém do Pará, Brazil, 2 • 57 ′ 29,47 ″ S/47 • 23 ′ 10,37 ″ W) were processed to obtain the hydro-alcoholic extract as previously described (Rocha et al 2007 HUVECs preserve endothelial cell native characteristics, including the expression of specific surface markers and intracellular signalling pathways. HUVECs were chosen as an experimental model in this study, since they have been a useful model to investigate endothelial dysfunction promoted by uraemic toxins (Dou et al 2004(Dou et al , 2007Faure et al 2006;Gross et al 2015;Lu et al 2016;Migliori et al 2015) and also other biological actions (Addi et al 2019;Shen et al 2016).…”

Section: Açaí Seed Extractmentioning

confidence: 99%

Uraemic toxin‐induced inflammation and oxidative stress in human endothelial cells: protective effect of polyphenol‐rich extract from açaí

Monteiro

Soares

Trindade

et al. 2020

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the central question of this study?Does a polyphenol‐rich extract from açaí have a potential role in preventing uraemic toxin‐induced endothelial cell dysfunction? What is the main finding and its importance?Polyphenols from açaí prevented cell death, restored migratory capacity, protected from inflammation and contributed to the restoration of the antioxidant response in endothelial cells exposed to uraemic toxins. The protective role of açaí against toxic effects exerted by uraemic toxins presents a potential new therapeutic target in endothelial cells. Abstract In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein‐bound uraemic toxins such as p‐cresyl sulfate (pCS) and indoxyl sulfate (IS). Among strategies to ameliorate the harmful actions of uraemic toxins, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti‐inflammatory actions of phenolic‐rich açaí seed extract (ASE) in response to endothelial dysfunction induced by IS and pCS, in human umbilical vein endothelial cells (HUVECs). Cells were treated with ASE (10 µg ml−1) in the presence or absence of IS (61 µg ml−1) and pCS (40 µg ml−1). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes, and oxidative damage was evaluated. IS and pCS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (P < 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up‐regulated pro‐inflammatory cytokine expression, and ASE was able to beneficially counteract this effect. Tumour necrosis factor‐α secretion was greater in uraemic toxin‐treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (P < 0.05). With regard to the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (P < 0.05). From the results, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uraemic toxins (particularly by IS) in human endothelial cells.

show abstract

Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells

Cited by 55 publications

References 65 publications

Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy

Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy

Chronodisruption: A Poorly Recognized Feature of CKD

Uraemic toxin‐induced inflammation and oxidative stress in human endothelial cells: protective effect of polyphenol‐rich extract from açaí

Contact Info

Product

Resources

About