scholarly journals Secreted Frizzled-Related Protein 5 Ameliorates Vascular Calcification in a Rat Model of Chronic Kidney Disease through the Wnt/β-Catenin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Dai Deng ◽  
Xue Han ◽  
Zongli Diao ◽  
Wenhu Liu
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Rat Model ◽  
In Vitro Study ◽  
Calcium Content ◽  
Control Group ◽  
Related Protein ◽  
High Phosphate

<b><i>Introduction:</i></b> Vascular calcification (VC) is highly prevalent and a major cardiovascular risk factor in chronic kidney disease (CKD) patients. Secreted frizzled-related protein 5 (SFRP5), an inhibitor of the Wnt pathway, is an adipokine with a positive effect on metabolic and cardiovascular diseases. Our previous in vitro study showed that SFRP5 attenuates high phosphate-induced calcification in vascular smooth muscle cells by inhibiting the Wnt/β-catenin pathway. Therefore, we hypothesized that SFRP5 may protect against CKD-associated VC (CKD-VC) through the same signalling. <b><i>Methods:</i></b> The rat model of CKD with VC was induced by 0.75% adenine combined with 1.8% high phosphate diet, which were administered with adenovirus vectors of SFRP5. We evaluated the SFRP5 effect on VC by von Kossa staining and calcium content analysis and osteogenic markers by immunohistochemistry and Western blot. The components of Wnt/ß-catenin signalling were also evaluated. <b><i>Results:</i></b> SFRP5 local and serum levels were significantly decreased in the CKD-VC rat model compared with the control group. Adenovirus-mediated overexpression of SFRP5 significantly inhibited VC, which was due to suppression of CKD-induced expression of calcification and osteoblastic markers. Additionally, SFRP5 abrogated activation of the Wnt/β-catenin pathway that plays a major role in the pathogenesis of VC. The specificity of SFRP5 for inhibition of VC was confirmed using an empty adenovirus as a control. <b><i>Conclusion:</i></b> Our results suggest that SFRP5 ameliorates VC of CKD rats by inhibiting the expression of calcification and osteoblastic markers as well as the Wnt/β-catenin pathway. Collectively, this study suggests that SFRP5 is a potential therapeutic target in CKD-VC.

scholarly journals Reduction of Secreted Frizzled-Related Protein 5 Drives Vascular Calcification through Wnt3a-Mediated Rho/ROCK/JNK Signaling in Chronic Kidney Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3539 ◽  
Author(s):  
Yun Jung Oh ◽  
Hyunsook Kim ◽  
Ae Jin Kim ◽  
Han Ro ◽  
Jae Hyun Chang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Loss ◽  
Vascular Calcification ◽  
Rat Model ◽  
Integration Site ◽  
Wnt Signaling Pathway ◽  
Coiled Coil ◽  
Control Group ◽  
Related Protein

Vascular calcification (VC) is commonly associated with bone loss in patients with chronic kidney disease (CKD). The Wingless-related integration site (Wnt) regulates osteoblast activation through canonical signaling pathways, but the common pathophysiology of these pathways during VC and bone loss has not been identified. A rat model of adenine-induced CKD with VC was used in this study. The rats were fed 0.75% adenine (2.5% protein, 0.92% phosphate) with or without intraperitoneal injection of calcitriol (0.08 µg/kg/day) for 4 weeks. Angiotensin II (3 µM)-induced VC was achieved in high phosphate medium (3 mM) through its effect on vascular smooth muscle cells (VSMCs). In an mRNA profiler polymerase chain reaction assay of the Wnt signaling pathway, secreted frizzled-related protein 5 (sFRP5) levels were significantly decreased in the CKD rat model compared with the control group. The repression of sFRP5 on VSMC trans-differentiation was mediated through Rho/Rho-associated coiled coil containing protein kinase (ROCK) and c-Jun N-terminal kinase (JNK) pathways activated by Wnt3a. In a proof of concept study conducted with patients with CKD, serum sFRP5 concentrations were significantly lower in subjects with VC than in those without VC. Our findings suggest that repression of sFRP5 is associated with VC in the CKD environment via activation of the noncanonical Wnt pathway, and thus that sFRP5 might be a novel therapeutic target for VC in CKD.

Receptor for advanced glycation end products: a key molecule in the genesis of chronic kidney disease vascular calcification and a potential modulator of sodium phosphate co-transporter PIT-1 expression

2019 ◽  
Vol 34 (12) ◽  
pp. 2018-2030 ◽  
Author(s):  
Karim Belmokhtar ◽  
Jeremy Ortillon ◽  
Stéphane Jaisson ◽  
Ziad A Massy ◽  
Camille Boulagnon Rombi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Advanced Glycation End Products ◽  
Mrna Levels ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
High Phosphate

Abstract Background Chronic kidney disease (CKD) is associated with increased cardiovascular mortality, frequent vascular calcification (VC) and accumulation of uraemic toxins. Advanced glycation end products and S100 proteins interact with the receptor for advanced glycation end products (RAGE). In the present work, we aimed to investigate the role(s) of RAGE in the CKD–VC process. Methods Apoe−/− or Apoe−/−Ager (RAGE)−/− male mice were assigned to CKD or sham-operated groups. A high-phosphate diet was given to a subgroup of Apoe−/−and Apoe−/−Ager−/− CKD mice. Primary cultures of Ager+/+ and Ager−/− vascular smooth muscle cells (VSMCs) were established and stimulated with either vehicle, inorganic phosphate (Pi) or RAGE ligands (S100A12; 20 µM). Results After 12 weeks of CKD we observed a significant increase in RAGE ligand (AGE and S100 proteins) concentrations in the serum of CKD Apoe−/− mice. Ager messenger RNA (mRNA) levels were 4-fold higher in CKD vessels of Apoe−/− mice. CKD Apoe−/− but not CKD Apoe−/− or Ager−/− mice displayed a marked increase in the VC surface area. Similar trends were found in the high-phosphate diet condition. mRNA levels of Runx2 significantly increased in the Apoe−/− CKD group. In vitro, stimulation of Ager+/+VSMCs with Pi or S100A12 induced mineralization and osteoblast transformation, and this was inhibited by phosphonoformic acid (Pi co-transporters inhibitor) and Ager deletion. In vivo and in vitro RAGE was necessary for regulation of the expression of Pit-1, at least in part through production of reactive oxygen species. Conclusion RAGE, through the modulation of Pit-1 expression, is a key molecule in the genesis of VC.

scholarly journals Effect of cross-linked chitosan iron (III) on vascular calcification in uremic rats

2018 ◽  
Vol 243 (9) ◽  
pp. 796-802 ◽  
Author(s):  
Barbara Bruna Abreu de Castro ◽  
Wander Barros do Carmo ◽  
Paulo Giovani de Albuquerque Suassuna ◽  
Moises Carminatti ◽  
Julia Bianchi Brito ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Carbonate ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Fibroblast Growth Factor 23 ◽  
Calcium Content ◽  
Control Group ◽  
Fibroblast Growth ◽  
Phosphorus Excretion ◽  
Chelating Effect

Cross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups. We measured creatinine, phosphorus, calcium, alkaline phosphatase, phosphorus excretion fraction, parathyroid hormone, and fibroblast growth factor 23. Vascular calcification was assessed using the aortic calcium content, and a semi-quantitative analysis was performed using Von Kossa and hematoxylin–eosin staining. At week seven, rats in the chronic kidney disease group had higher creatinine, phosphorus, phosphorus excretion fraction, calcium, alkaline phosphatase, fibroblast growth factor 23, and aortic calcium content than those in the Control group. Treatments with cross-linked chitosan iron (III) and calcium carbonate prevented phosphorus increase (20%–30% reduction). The aortic calcium content was lowered by 88% and 85% in the CKD-Ch and CKD-sevelamer groups, respectively. The prevalence of vascular changes was higher in the chronic kidney disease and CKD-calcium carbonate (62.5%) groups than in the CKD-Ch group (37.5%). In conclusion, cross-linked chitosan iron (III) had a phosphorus chelating effect similar to calcium carbonate already available for clinical use, and prevented calcium accumulation in the aorta. Impact statement Vascular calcification (VC) is a common complication due to CKD-related bone and mineral disorder (BMD) and is characterized by deposition of calcium in vessels. Effective therapies are not yet available but new phosphorus chelators can prevent complications from CV. We tested the effect of chitosan, a new phosphorus chelator, on the VC of uremic animals. It has recently been proposed that chitosan treatment may be effective in the treatment of hyperphosphataemia. However, its action on vascular calcification has not been investigated yet. In this study, we demonstrated that chitosan reduced the calcium content in the aorta, suggesting that this may be a therapeutic approach in the treatment of hyperphosphatemia by preventing CV.

Does Vitamin K Intake Influence High Phosphate Induced Vascular Pseudo-ossification: An Underappreciated Therapeutic Prospect in General Population?

2019 ◽  
Vol 20 (4) ◽  
pp. 421-430
Author(s):  
Zar Chi Thent ◽  
Gabriele R.A. Froemming ◽  
Suhaila Abd Muid
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Prolonged Exposure ◽  
Vascular Complication ◽  
Key Factors ◽  
The Matrix ◽  
Underlying Mechanisms ◽  
High Phosphate

Increasing interest in vascular pseudo-ossification has alarmed the modern atherosclerotic society. High phosphate is one of the key factors in vascular pseudo ossification, also known as vascular calcification. The active process of deposition of the phosphate crystals in vascular tissues results in arterial stiffness. High phosphate condition is mainly observed in chronic kidney disease patients. However, prolonged exposure with high phosphate enriched foods such as canned drinks, dietary foods, etc. can be considered as modifiable risk factors for vascular complication in a population regardless of chronic kidney disease. High intake of vitamin K regulates the vascular calcification by exerting its anti-calcification effect. The changes in serum phosphate and vitamin K levels in a normal individual with high phosphate intake are not well investigated. This review summarised the underlying mechanisms of high phosphate induced vascular pseudo ossification such as vascular transdifferentiation, vascular apoptosis and phosphate uptake by sodium-dependent co-transporters. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google Scholar were searched using the terms ‘vitamin K’, ‘vascular calcification, ‘phosphate’, ‘transdifferentiation’ and ‘vascular pseudoossification’. Vitamin K certainly activates the matrix GIA protein and inhibits vascular transition and apoptosis in vascular pseudo-ossification. The present view highlighted the possible therapeutic linkage between vitamin K and the disease. Understanding the role of vitamin K will be considered as potent prophylaxis agent against the vascular disease in near future.

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.

scholarly journals Calciprotein particle inhibition explains magnesium-mediated protection against vascular calcification

2019 ◽  
Vol 35 (5) ◽  
pp. 765-773 ◽  
Author(s):  
Anique D ter Braake ◽  
Coby Eelderink ◽  
Lara W Zeper ◽  
Andreas Pasch ◽  
Stephan J L Bakker ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Healthy Controls ◽  
Gene And Protein Expression ◽  
Calciprotein Particles

Abstract Background Phosphate (Pi) toxicity is a strong determinant of vascular calcification development in chronic kidney disease (CKD). Magnesium (Mg2+) may improve cardiovascular risk via vascular calcification. The mechanism by which Mg2+ counteracts vascular calcification remains incompletely described. Here we investigated the effects of Mg2+ on Pi and secondary crystalline calciprotein particles (CPP2)-induced calcification and crystal maturation. Methods Vascular smooth muscle cells (VSMCs) were treated with high Pi or CPP2 and supplemented with Mg2+ to study cellular calcification. The effect of Mg2+ on CPP maturation, morphology and composition was studied by medium absorbance, electron microscopy and energy dispersive spectroscopy. To translate our findings to CKD patients, the effects of Mg2+ on calcification propensity (T50) were measured in sera from CKD patients and healthy controls. Results Mg2+ supplementation prevented Pi-induced calcification in VSMCs. Mg2+ dose-dependently delayed the maturation of primary CPP1 to CPP2 in vitro. Mg2+ did not prevent calcification and associated gene and protein expression when added to already formed CPP2. Confirmatory experiments in human serum demonstrated that the addition of 0.2 mmol/L Mg2+ increased T50 from healthy controls by 51 ± 15 min (P &lt; 0.05) and CKD patients by 44 ± 13 min (P &lt; 0.05). Each further 0.2 mmol/L addition of Mg2+ led to further increases in both groups. Conclusions Our results demonstrate that crystalline CPP2 mediates Pi-induced calcification in VSMCs. In vitro, Mg2+ delays crystalline CPP2 formation and thereby prevents Pi-induced calcification.

OGT knockdown counteracts high phosphate-induced vascular calcification in chronic kidney disease through autophagy activation by downregulating YAP

Life Sciences ◽  
2020 ◽  
Vol 261 ◽  
pp. 118121 ◽  
Author(s):  
Tian-Hua Xu ◽  
Zitong Sheng ◽  
Yue Li ◽  
Xiaobo Qiu ◽  
Binyao Tian ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
High Phosphate

Endothelial damage and vascular calcification in patients with chronic kidney disease

2014 ◽  
Vol 307 (11) ◽  
pp. F1302-F1311 ◽  
Author(s):  
Sagrario Soriano ◽  
Andrés Carmona ◽  
Francisco Triviño ◽  
Mariano Rodriguez ◽  
Marina Alvarez-Benito ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Endothelial Damage ◽  
Endothelial Microparticles ◽  
Healthy Donors ◽  
Cardiovascular Morbidity And Mortality

Vascular calcification (VC) is a frequent complication of chronic kidney disease (CKD) and is a predictor of cardiovascular morbidity and mortality. In the present study, we investigated the potential involvement of endothelial microparticles (MPs) and endothelial progenitor cells (EPCs) in the generation of VC in CKD patients. The number of circulating EMPs is greater in patients with VC than without VC (307 ± 167 vs. 99 ± 75 EMPs/μl, P < 0.001). The percentage of EPCs is significantly lower in patient with VC than in patients without VC (0.14 ± 0.11% vs. 0.25 ± 0.18%, P = 0.002). The number of EPCs expressing osteocalcin (OCN) was higher in VC patients (349 ± 63 cells/100,000) than in non-VC patients (139 ± 75 cells/100,000, P < 0.01). In vitro, MPs obtained from CKD patients were able to induce OCN expression in EPCs from healthy donors; the increase in OCN expression was more accentuated if MPs were obtained from CKD patients with VC. MPs from CKD patients also induced OCN expression in vascular smooth muscle cells and fibroblasts. In CKD patients, the rise in endothelial MPs associated with a decrease in the number of EPCs, suggesting an imbalance in the processes of endothelial damage and repair in CKD patients, mainly those with VC. Our results suggest that EPCs, through OCN expression, may directly participate in the process of VC.

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 Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1156
Author(s):  
Aikaterini Lysitska ◽  
Nikiforos Galanis ◽  
Ioannis Skandalos ◽  
Christina Nikolaidou ◽  
Sophia Briza ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Morphometric Analysis ◽  
Intima Media Thickness ◽  
Inflammatory Cells ◽  
Vascular Wall ◽  
Control Group ◽  
Group A ◽  
Group B

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p < 0.0001, and, with intima-media thickness (IMT), the severity of RANKL expression R2 = 0.3, p < 0.0001. Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall.

Sign in / Sign up

Export Citation Format

Share Document