Unfavorable Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: The Role of Oxidative Stress

Roumeliotis, Stefanos; Dounousi, Evangelia; Salmas, Marios; Eleftheriadis, Theodoros; Liakopoulos, Vassilios

doi:10.3390/biom10050768

Cited by 49 publications

(55 citation statements)

References 86 publications

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“…These findings confirm ROS, and specifically mtROS, as key mediators in the process of PD-mediated EMT. These results are consistent with in vitro studies in other cell types, and also in mesothelial cells, showing that TGF-β1 also increases the generation of mtROS, resulting in inflammatory response, phenotype transition and, finally, fibrosis [ 19 , 20 , 29 , 33 ]. On the other hand, we also observed a significant decrease of mitochondrial membrane potential in cells affected by EMT.…”

Section: Discussionsupporting

confidence: 89%

“…There is a clear connection between mitochondrial damage, oxidative stress and inflammation [ 21 , 28 ], as well as between chronic inflammation and fibrosis, including peritoneal fibrosis [ 10 , 29 ]. According to this point of view, inflammation could antedate membrane fibrosis, and even the relationship between these two processes could be bidirectional, each one inducing the other [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

et al. 2021

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Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

et al. 2021

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“…They accumulate with rising age and contributing factors such as hyperglycemia, hyperlipidemia, oxidative stress and other illnesses which affect the renal system [ 60 , 61 ]. Several studies pointed to a strong association between oxidative stress and the level of AGEs [ 20 , 21 , 22 ]. Moreover, with AGEs’ association with inflammation, oxidative stress and uremic state due to CKD, it could be hypothesized that all of these factors cumulatively contribute to cardiovascular mortality and morbidity in CKD/HD patients.…”

Section: Discussionmentioning

confidence: 99%

“…During the heat sterilization process of the PD fluids, glucose degradation products are accumulated in the peritoneum and they trigger the formation of AGEs in excessive amounts, leading to an increased oxidative stress [ 20 ]. During HD, it was shown that the reactive carbonyl compounds accumulated due to renal failure and the interaction of blood with the dialysis membrane, both contributing to an amplified formation of AGEs [ 15 , 21 ]. Consequential formation of oxidative products, loss of important antioxidants and chronic inflammation are the most significant factors that lead to high cardiovascular risk and increased mortality in CKD/HD settings [ 11 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma Catestatin Levels and Advanced Glycation End Products in Patients on Hemodialysis

et al. 2021

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Catestatin (CST) is a pleiotropic peptide involved in cardiovascular protection with its antihypertensive and angiogenic effects. Considering that patients with end-stage renal disease (ESRD) who are undergoing hemodialysis (HD) are associated with higher cardiovascular risk, the aim of this study was to investigate plasma CST levels in HD patients, compare them to healthy controls and evaluate possible CST associations with advanced glycation end products (AGEs) and laboratory, anthropometric and clinical parameters. The study included 91 patients on HD and 70 healthy controls. Plasma CST levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit, while AGEs were determined using skin autofluorescence. Plasma CST levels were significantly higher in the HD group compared to the controls (32.85 ± 20.18 vs. 5.39 ± 1.24 ng/mL, p < 0.001) and there was a significant positive correlation between CST and AGEs (r = 0.492, p < 0.001). Furthermore, there was a significant positive correlation between plasma CST levels with both the Dialysis Malnutrition Score (r = 0.295, p = 0.004) and Malnutrition-Inflammation Score (r = 0.290, p = 0.005). These results suggest that CST could be playing a role in the complex pathophysiology of ESRD/HD and that it could affect the higher cardiovascular risk of patients on HD.

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“…The peritoneum is composed of a monolayer of mesothelial cells, supported by connective tissue, underneath of which there are blood vessels, nerves, and lymphatic vessels. In long-term PD, the PM serves as a semipermeable barrier for ultrafiltration, and diffusion may present structural alterations, including peritoneal fibrosis (PF), vasculopathy, and angiogenesis, which are leading causes of peritoneal ultrafiltration failure (Roumeliotis et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Tetramethylpyrazine Ameliorates Peritoneal Angiogenesis by Regulating VEGF/Hippo/YAP Signaling

Zhu

Shan

et al. 2021

Front. Pharmacol.

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Angiogenesis of human peritoneal vascular endothelial cells (HPVECs), linked to vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling, is a complication of peritoneal fibrosis (PF). Hippo/YAP signaling interacts with VEGF/VEGFR2 signaling, but the effect on peritoneal angiogenesis and PF has not been studied. We tested VEGF/Hippo/YAP inhibition by tetramethylpyrazine (TMP) in PF mice and HPVECs. This treatment ameliorated peritoneal dialysis (PD)–induced angiogenesis and PF. In mice, PF was associated with upregulation of VEGF, and TMP ameliorated submesothelial fibrosis, perivascular bleeding, and Collagen I abundance. In HPVECs, angiogenesis occurred due to human peritoneal mesothelial cells (HPMCs)–conditioned medium, and TMP alleviated HPVECs migration, tube formation, and YAP nuclear translocation. YAP knockdown PF mouse and HPVEC models were established to further confirm our finding. YAP deletion attenuated the PD-induced or VEGF-induced increase in angiogenesis and PF. The amount of CYR61 and CTGF was significantly less in the YAP knockdown group. To study the possibility that TMP could benefit angiogenesis, we measured the HPVECs migration and tube formation and found that both were sharply increased in YAP overexpression; TMP treatment partly abolished these increases. As well, the amount of VEGFR localized in the trans-Golgi network was lower by double immunofluorescence; VEGFR and its downstream signaling pathways including p-ERK, p-P38, and p-Akt were more in HPVECs with YAP overexpression. Overall, TMP treatment ameliorated angiogenesis, PF, and peritoneum injury. These changes were accompanied by inhibition of VEGF/Hippo/YAP.

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Unfavorable Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: The Role of Oxidative Stress

Cited by 49 publications

References 86 publications

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

Mitochondrial Dysfunction Plays a Relevant Role in Pathophysiology of Peritoneal Membrane Damage Induced by Peritoneal Dialysis

Plasma Catestatin Levels and Advanced Glycation End Products in Patients on Hemodialysis

Tetramethylpyrazine Ameliorates Peritoneal Angiogenesis by Regulating VEGF/Hippo/YAP Signaling

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