Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction

Carmona, Andrés; Guerrero, Fatima; Buendía, Paula; Obrero, Teresa; Aljama, Pedro; Carracedo, Julia

doi:10.3389/fphys.2017.00666

Cited by 60 publications

(67 citation statements)

References 58 publications

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“…Endothelial MVs can serve as useful biomarkers of CKD (Carmona et al, 2017a) because endothelial damage is associated with CKD, and the release of EVs is enhanced during endothelial injury. Uremic toxins (such as IS) also induce a release of endothelial MVs (Carmona et al, 2017b). Not only are plasma EVs modified in kidney diseases, but the release of EVs from renal cells (epithelial cells, podocytes, and tubular cells) is also altered.…”

Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

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Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremiaassociated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.

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Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

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“…IS decreases endothelial progenitor cell proliferation, increases endothelial progenitor cell senescence, induces oxidative stress via a NO dependent pathway and alters endothelial progenitor cell mobilization and angiogenesis. Carmona et al [82] described endothelial progenitor cell senescence induced by IS via p53 and NF-κB activation reducing the ability to form new vessels. In endothelial progenitor cells, IS decreases VEGF production in response to hypoxia [65].…”

Section: Indoxyl Sulfate a Uremic Endotheliotoxin: Molecular Mechanismsmentioning

confidence: 99%

Indoxyl Sulfate, a Uremic Endotheliotoxin

Lano

Burtey

Sallée

2020

Toxins

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Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)—derived from tryptophan metabolism—accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial dysfunction implicated in cardiovascular morbidity and mortality during CKD. In this review, we describe clinical and experimental evidence for IS endothelial toxicity and focus on the various molecular pathways implicated. In patients with CKD, plasma concentrations of IS correlate with cardiovascular events and mortality, with vascular calcification and atherosclerotic markers. Moreover, IS induces a prothrombotic state and impaired neovascularization. IS reduction by AST-120 reverse these abnormalities. In vitro, IS induces endothelial aryl hydrocarbon receptor (AhR) activation and proinflammatory transcription factors as NF-κB or AP-1. IS has a prooxidant effect with reduction of nitric oxide (NO) bioavailability. Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients.

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“…According to a previous model of endothelial damage using different doses of IS to mediate oxidative stress in endothelial cells, the dose of IS 256 µg/mL was optimal to induce cell activation without producing toxicity and cell death [33]. After performing a dose-response study to analyze the cellular viability, we selected the dose of IS at 256 µg/mL to induce cell activation in THP-1 monocytes.…”

Section: Culture Of Human Monocytes (Thp-1)mentioning

confidence: 99%

Increasing the Magnesium Concentration in Various Dialysate Solutions Differentially Modulates Oxidative Stress in a Human Monocyte Cell Line

et al. 2020

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es (M.A.) † These authors share senior authorship.Abstract: Oxidative stress is exacerbated in hemodialysis patients by several factors, including the uremic environment and the use of dialysis fluids (DFs). Since magnesium (Mg) plays a key role in modulating immune function and in reducing oxidative stress, we aimed to evaluate whether increasing the Mg concentration in different DFs could protect against oxidative stress in immunocompetent cells in vitro. Effect of ADF (acetate 3 mM), CDF (citrate 1 mM), and ACDF (citrate 0.8 mM + acetate 0.3 mM) dialysates with Mg at standard (0.5 mM) or higher (1, 1.25, and 2 mM) concentrations were assessed in THP-1 monocyte cultures. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were quantified under basal and uremic conditions (indoxyl sulfate (IS) treatment). Under uremic conditions, the three DFs with 0.5 mM Mg promoted higher ROS production and lipid damage than the control solution. However, CDF and ACDF induced lower levels of ROS and MDA, compared to that induced by ADF. High Mg concentration (1.25 and/or 2 mM) in CDF and ACDF protected against oxidative stress, indicated by reduced ROS and MDA levels compared to respective DFs with standard concentration of Mg. Increasing Mg concentrations in ADF promoted high ROS production and MDA content. Thus, an increase in Mg content in DFs has differential effects on the oxidative stress in IS-treated THP-1 cells depending on the dialysate used. renal function and the prevalence of cardiovascular events through altered leukocyte activation and intensified oxidative stress [3][4][5][6][7].Classically, UTs are divided into three categories: low-molecular-weight water-soluble solutes (<500 Da), middle-molecular-weight solutes (>500 Da), and protein-bound solutes [8]. These uremic toxins, represented by IS, is extremely toxic and difficult to eliminate by conventional dialysis; consequently, high IS levels may trigger oxidative-inflammatory stress, playing a key pathophysiologic role in CKD. In fact, several studies have confirmed that the occurrence of CVD induced by CKD is closely related to the IS accumulation [3].Uremia promotes a state of enhanced oxidative stress, which is the result of pro-oxidant molecules, such as reactive oxygen species (ROS), overwhelming the antioxidant defense mechanisms [9]. An increase in oxidative stress occurs during the dialysis session owing to the loss of antioxidants (e.g., uric acid, etc.) and the activation of leukocytes, which trigger both inflammatory compounds and ROS production, contributing to oxidative damage of biomolecules (e.g., lipid peroxidation, DNA damage, etc.) [3,[9][10][11][12].Clinical and experimental evidence demonstrates that several factors inherent to the dialysis procedure itself, such as dialysis modality, iron administration, biocompatibility, and types of dialyzer membrane and dialysates, can play a key role promoting chronic inflammation and oxidative stress in HD patients [9][10][11][12]. Bio-incompatibility during HD induces leukocyte activation...

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Microvesicles Derived from Indoxyl Sulfate Treated Endothelial Cells Induce Endothelial Progenitor Cells Dysfunction

Cited by 60 publications

References 58 publications

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Indoxyl Sulfate, a Uremic Endotheliotoxin

Increasing the Magnesium Concentration in Various Dialysate Solutions Differentially Modulates Oxidative Stress in a Human Monocyte Cell Line

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