scholarly journals The antioxidant tempol ameliorates arterial medial calcification in uremic rats: Important role of oxidative stress in the pathogenesis of vascular calcification in chronic kidney disease

2012 ◽  
Vol 27 (2) ◽  
pp. 474-485 ◽  
Author(s):  
Shunsuke Yamada ◽  
Masatomo Taniguchi ◽  
Masanori Tokumoto ◽  
Jiro Toyonaga ◽  
Kiichiro Fujisaki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Arterial Medial Calcification ◽  
Medial Calcification

scholarly journals P0690CORRELATIONS BETWEEN OPG/RANKL/RANK AXIS, VITAMIN D STATUS, PTH AND VASCULAR CALCIFICATION IN AN ADENINE-INDUCED MODEL OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beata Sieklucka ◽  
Tomasz Domaniewski ◽  
Marta Zieminska ◽  
Malgorzata Galazyn-Sidorczuk ◽  
Anna Pawlak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Control Group ◽  
Urea Nitrogen ◽  
And Control ◽  
Rank Gene

Abstract Background and Aims Chronic kidney disease (CKD) is a major public health problem worldwide and refers to a wide range of disorders in bone and mineral metabolism, abnormalities of biochemical parameters and pathological calcification of the blood vessels. Vascular calcification (VC) is a common complication in CKD patients, contributes to cardiovascular disease (CVD), and associates with increased mortality and morbidity. The precise mechanism of VC in CKD is not yet fully understood. Recently discovered molecules such as osteoprotegerin (OPG), its ligand receptor activator of nuclear factor NF-κB ligand (RANKL) and RANK are not only well-known to play a crucial role in bone homeostasis, but they has also been implicated in the process of development of vascular complications However the exact role of OPG/RANKL/RANK axis in the process of VC has not been yet fully assessed. Thus, the aim of this work is to evaluate the role of OPG/RANKL/RANK axis in the process of calcification in CKD. Method Seventy two male Wistar rats weighing 260-290 g (8-weeks old) were initially divided into 6 groups containing 12 animals in each group. Rats were divided into six groups: control rats (K4, K6, K8) and CKD rats (B4, B6, B8). Control group rats received standard diet, whereas CKD rats were fed a low adenine – diet containing 0.3 % adenine, 1.0 % Ca, 1.2 % Pi through 4 (K4, B4), 6 (K6, B6) and 8 (K8, B8) weeks. Subsequently, CKD and control rats were sacrificed at weeks 4 (n=24), 6 (n=24) and 8 (n=24). One day before being killed, the rats were placed in metabolic cages for 24-hour urine collection. Thereafter, the rats were anesthetized and samples of blood, as well as aortas were collected. Next, the OPG, RANKL, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxy vitamin D3 1,25(OH)2D3 concentrations were determined using appropriate ELISA kits. Then the sRANKL/OPG ratio was calculated. The OPG, RANK and RANKL gene expression was assessed using real-time PCR (RT-PCR). The VC was quantified by measurement of the arterial calcium (Ca) and phosphate (Pi) content using flame atomic absorption. Serum levels of urea nitrogen, creatinine, uric acid, Ca, Pi and urinary levels of creatinine, Ca and Pi were measured. Results There was a progressive increase in serum urea nitrogen, creatinine, uric acid and PTH of CKD rats in comparison to control values. We also observed significantly decreased levels of 25(OH)D, 1,25(OH)2D and serum Ca. Total Ca content in the aorta was significantly increased in CKD rats in comparison with control group, whereas total Pi content in the aorta was significantly increased only in B8 group in comparison to appropriate controls. There were no differences in serum OPG and sRANKL levels between CKD and control rats. In contrast, we observed decreased OPG, RANKL and RANK gene expression in a B4 group in comparison to appropriate controls, whereas in a B6 group we noticed increased OPG, RANKL and decreased RANK gene expression. B8 group revealed increased RANKL and RANK gene expression, but there were no differences in OPG gene expression between CKD rats and control group. Furthermore, we observed positive correlations between serum sRANKL and OPG and RANK gene expression. Ca and P content in the aorta inversely corelated with RANKL gene expression, whereas positively with OPG gene expression. Serum 25(OH)D concentrations correlated inversely with Ca in aorta. PTH was positively correlated with serum RANKL and OPG and gene expression these cytokines. Conclusion Our results suggest that OPG/RANK/RANKL axis may be involved in the process of vascular calcification in chronic kidney disease. However, its role and evaluation of precise mechanism in this field requires further evaluation.

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis

2018 ◽  
Vol 234 (7) ◽  
pp. 11411-11423 ◽  
Author(s):  
Mohammad Khabbaz Shirazi ◽  
Asaad Azarnezhad ◽  
Mohammad Foad Abazari ◽  
Mansour Poorebrahim ◽  
Pegah Ghoraeian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Hydrogen Sulfide ◽  
Kidney Disease ◽  
Nitric Oxide Signaling

Role of matrix metalloproteinase-9 in chronic kidney disease: a new biomarker of resistant albuminuria

2016 ◽  
Vol 130 (7) ◽  
pp. 525-538 ◽  
Author(s):  
Helena Pulido-Olmo ◽  
Concha F. García-Prieto ◽  
Gloria Álvarez-Llamas ◽  
María G. Barderas ◽  
Fernando Vivanco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

Resistant albuminuria developed under chronic RAS blockade is strongly associated with increased circulating MMP-9 activity mediated by oxidative stress.

scholarly journals Magnesium Attenuates Phosphate-Induced Deregulation of a MicroRNA Signature and Prevents Modulation of Smad1 and Osterix during the Course of Vascular Calcification

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Loïc Louvet ◽  
Laurent Metzinger ◽  
Janine Büchel ◽  
Sonja Steppan ◽  
Ziad A. Massy
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Inorganic Phosphate ◽  
Time Course ◽  
Mechanistic Explanation ◽  
High Phosphate

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease (CKD). High phosphate levels promote VC by inducing abnormalities in mineral and bone metabolism. Previously, we demonstrated that magnesium (Mg2+) prevents inorganic phosphate- (Pi-) induced VC in human aortic vascular smooth muscle cells (HAVSMC). As microRNAs (miR) modulate gene expression, we investigated the role of miR-29b, -30b, -125b, -133a, -143, and -204 in the protective effect of Mg2+on VC. HAVSMC were cultured in the presence of 3 mM Pi with or without 2 mM Mg2+chloride. Total RNA was extracted after 4 h, 24 h, day 3, day 7, and day 10. miR-30b, -133a, and -143 were downregulated during the time course of Pi-induced VC, whereas the addition of Mg2+restored (miR-30b) or improved (miR-133a, miR-143) their expression. The expression of specific targets Smad1 and Osterix was significantly increased in the presence of Pi and restored by coincubation with Mg2+. As miR-30b, miR-133a, and miR-143 are negatively regulated by Pi and restored by Mg2+with a congruent modulation of their known targets Runx2, Smad1, and Osterix, our results provide a potential mechanistic explanation of the observed upregulation of these master switches of osteogenesis during the course of VC.

scholarly journals FP450THE ROLE OF APELIN IN VASCULAR CALCIFICATION IN TYPE 2 DIABETES IN THE EARLY STAGES OF CHRONIC KIDNEY DISEASE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Ana Paula Silva ◽  
Mendes Filipa ◽  
Carias Eduarda ◽  
Fragoso Andre ◽  
Almeida Edgar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Early Stages

scholarly journals Role of gut-derived uremic toxins on oxidative stress and inflammation in patients with chronic kidney disease

2017 ◽  
Vol 27 (5) ◽  
pp. 359 ◽  
Author(s):  
P. V. L. N.Srinivasa Rao ◽  
S Gouroju ◽  
AR Bitla ◽  
KS Vinapamula ◽  
SM Manohar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Uremic Toxins

Abstract 17021: A Novel Human Relaxin Receptor Agonist, ML290, Attenuates Atherosclerosis- and Chronic Kidney Disease-Induced Vascular Calcification in Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hooi Hooi Ng ◽  
Daniela Medina ◽  
Alexander I Agoulnik ◽  
Joshua Hutcheson
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Therapeutic Potential ◽  
Superoxide Production ◽  
Scaffolding Protein ◽  
Cardiovascular Morbidity And Mortality ◽  
Relaxin Receptor ◽  
Medial Calcification

Introduction: Vascular calcification is the most significant predictor of cardiovascular morbidity and mortality, but therapeutic options are unavailable. Relaxin has emerged as a vasoprotective molecule, but several drawbacks prevent therapeutic translation. Targeting the relaxin receptor, RXFP1, is safe and well-tolerated in animal models of vascular disease and humans. We identified a biased allosteric agonist of human RXFP1, ML290, and aimed to test the hypothesis that ML290 arrests the progression of vascular calcification in mouse models of atherosclerosis and chronic kidney disease (CKD). Methods and Results: Recurrent treatment with ML290 significantly prevented ( P = 0.0422, n = 8) and reversed ( P = 0.0489, n = 6) atherosclerotic calcification in humanized ( hRXFP1/hRXFP1 ) Apoe -/- mice fed an atherogenic diet. Longitudinal tracing of mineral formation in the aortic arch of these mice revealed the presence of mineral in vehicle- but not ML290-treated mice after 15 weeks of diet. Accelerated mineral growth was observed in vehicle-treated mice after 20 weeks of the diet, which was reduced by ML290 treatment. In humanized mice with CKD, ML290 significantly prevented ( P = 0.0344, n = 9) medial calcification. In vitro , ML290 reduced ( P = 0.0005, n = 3) superoxide production under osteogenic conditions in vascular smooth muscle cells (VSMCs). Osteogenic changes in VSMC phenotype associate with a release of alkaline phosphatase (ALP) in extracellular vesicles (EVs), which promote mineralization. ML290 treatment significantly ( P = 0.0001, n = 3) suppressed the formation of ALP-loaded EVs in vitro . Bone morphogenetic protein-4, an inducer of osteogenic transitions, and caveolin-1, a scaffolding protein required for calcifying EV formation, were significantly ( P = 0.0059, n = 4) down-regulated after 24 h treatment with ML290 compared to vehicle-treated VSMCs under osteogenic conditions. Conclusions: We demonstrate the therapeutic potential for ML290 to mitigate atherosclerosis and CKD-induced vascular calcification in vivo . The actions of ML290 to prevent medial calcification are in part attributed to its ability to limit the release of calcifying EVs as a result of osteogenic differentiation, and to reduce vascular superoxide production.

Sign in / Sign up

Export Citation Format

Share Document