Inflammatory Cytokines and Reactive Oxygen Species as Mediators of Chronic Kidney Disease-Related Vascular Calcification

Agharazii, Mohsen; St-Louis, Ronald; Gautier-Bastien, Alexandra; Ung, Roth‐Visal; Mokas, Sophie; Lariviere, Richard W.; Richard, Darren E.

doi:10.1093/ajh/hpu225

Cited by 151 publications

(136 citation statements)

References 36 publications

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“…41 MMP-9 is secreted via inflammatory cells in the adventitia or smooth muscle cells. 42 In our study, a significant difference was found in the serum concentration of MMP-9 between nephrolithiasis patients and control group. Moreover, the significant increase was also found in the value of this biomarker within MMP-9/C1562T genotype T/T, TG and AG GG types in patients with nephrolithiasis.…”

Section: 35supporting

confidence: 44%

Association of MMP‐9 gene polymorphisms with nephrolithiasis patients

Mehde

Mehdi

Yusof

et al. 2017

Clinical Laboratory Analysis

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Background Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP‐9 with nephrolithiasis patients. Methods Genotyping of MMP‐9/R279Q and of MMP‐9/C1562T polymorphism were carried out by PCR‐based restriction digestion method. Serum level of MMP‐9, oxidative stress marker, MDA, and uric acid were measured in patients and control. Results Allele frequencies of the MMP‐9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP‐9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant. Conclusion The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP‐9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP‐9.

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Section: 35supporting

confidence: 44%

Association of MMP‐9 gene polymorphisms with nephrolithiasis patients

Mehde

Mehdi

Yusof

et al. 2017

Clinical Laboratory Analysis

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“…Phosphate up-regulates the expression of NOX4 and CYBA , two critical components of the superoxide-generating NADH/NADPH oxidase system [48, 49] and reduces total antioxidant capacity of VSMCs. Fibulin-3 supplementation is able to suppress the expression of NADH/NADPH oxidase system components and may, thus, interfere with reactive oxygen species production in VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress

Luong

Schelski

Boehme

et al. 2018

Cell Physiol Biochem

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Background/Aims: Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification. Methods: Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress. Results: Treatment with calcification medium significantly increased calcium deposition in HAoSMCs, an effect significantly blunted by additional treatment with Fibulin-3. Moreover, phosphate-induced alkaline phosphatase activity and mRNA expression of osteogenic and chondrogenic markers MSX2, CBFA1, SOX9 and ALPL were all significantly reduced by addition of Fibulin-3. These effects were paralleled by similar regulation of oxidative stress in HAoSMCs. Phosphate treatment significantly up-regulated mRNA expression of the oxidative stress markers NOX4 and CYBA, down-regulated total antioxidant capacity and increased the expression of downstream effectors of oxidative stress PAI-1, MMP2 and MMP9 as well as BAX/BLC2 ratio in HAoSMCs, all effects blocked by additional treatment with Fibulin-3. Furthermore, the protective effects of Fibulin-3 on phosphate-induced osteogenic and chondrogenic markers expression in HAoSMCs were reversed by additional treatment with hydrogen peroxide. Conclusions: Fibulin-3 attenuates phosphate-induced osteo-/ chondrogenic transdifferentiation and calcification of VSMCs, effects involving inhibition of oxidative stress. Up-regulation or supplementation of Fibulin-3 may be beneficial in reducing the progression of vascular calcification during hyperphosphatemic conditions such as CKD.

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“…Similarly, in CKD rat models, it was demonstrated that inflammation (TNF-␣, IL-1␤, IL-6) enhanced BMP2 and decreased SM ␣-actin expressions through activating MAPKs and phosphatidylinositol 3-kinase signaling pathways (2).…”

Section: The Possible Mechanisms For Mics-induced Ac In Ckdmentioning

confidence: 95%

MICS, an easily ignored contributor to arterial calcification in CKD patients

Zhang

Gao

Chen

et al. 2016

American Journal of Physiology-Renal Physiology

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In chronic kidney disease (CKD), simultaneous mineral and skeleton changes are prevalent, known as CKD-mineral bone disorder (CKD-MBD). Arterial calcification (AC) is a clinically important complication of CKD-MBD. It can increase arterial stiffness, which leads to severe cardiovascular events. However, current treatments have little effect on regression of AC, as its mechanisms are still unclear. There are multiple risk factors of AC, among which Malnutrition-Inflammation Complex Syndrome (MICS) is a new and crucial one. MICS, a combined syndrome of malnutrition and inflammation, generally begins at the early stage of CKD and becomes obvious in end-stage renal disease (ESRD). It was linked to reverse epidemiology and associated with increased cardiovascular mortality in ESRD patients. Recent data suggest that MICS can trigger CKD-MBD and accelerate the course of AC. In this present review, we summarize the recent understanding about the aggravating effects of MICS on AC and discuss the possible underlying mechanisms. A series of findings indicate that targeting MICS will provide a potential strategy for treating AC in CKD.

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Inflammatory Cytokines and Reactive Oxygen Species as Mediators of Chronic Kidney Disease-Related Vascular Calcification

Abstract: This study demonstrates a relationship between inflammation/ROS and arterial calcification in CKD and contributes to understanding of the complex pathways that mediate arterial calcification in CKD patients.

Cited by 151 publications

References 36 publications

Association of MMP‐9 gene polymorphisms with nephrolithiasis patients

Association of MMP‐9 gene polymorphisms with nephrolithiasis patients

Fibulin-3 Attenuates Phosphate-Induced Vascular Smooth Muscle Cell Calcification by Inhibition of Oxidative Stress

MICS, an easily ignored contributor to arterial calcification in CKD patients

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