IL-18 Mediates Vascular Calcification Induced by High-Fat Diet in Rats With Chronic Renal Failure

Objective: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality in patients with chronic renal failure (CRF). It is well-known that obesity and metabolic syndrome (OB/MS) predicts poor prognosis of CRF patients. However, the influence of OB/MS on VC in CRF patients isn't clear. IL-18 mediates OB/MS-related inflammation, but whether IL-18 is involved in OB/MS -mediated VC in CRF patients hasn't been studied. In this study, it was explored that whether OB/MS caused by high-fat diet (HFD) can affect the level of serum IL-18 and aggravate the degree of VC in CRF rats. Furthermore, it was studied that whether IL-18 induces rat vascular smooth muscle cells (VSMCs) calcification by activating the MAPK pathways.Approach: The rats were randomly assigned to the sham-operated, CRF and CRF + HFD groups. CRF was induced by 5/6 nephrectomy. Serum IL-18 levels and aortic calcification indicators were compared in each group. Primary rat VSMCs calcification were induced by β-glycerophosphate and exposed to IL-18. VSMCs were also treated with MAPK inhibitors.Results: The weight, serum levels of hsCRP, TG and LDL-C in CRF + HFD group were significantly higher than those in sham-operated and CRF groups (p < 0.05). Compared with the sham-operated group, the calcium content and the expression of BMP-2 of aorta in CRF and CRF + HFD groups were significantly increased (p < 0.05). Moreover, the calcium content and the expression of BMP-2 of aorta in CRF + HFD group was significantly higher than those in CRF group (p < 0.05). And the serum IL-18 level was positively correlated with aortic calcium content. It was also found that p38 inhibitor SB203580 can suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18. But the JNK inhibitor SP600125 can't suppress the VSMCs calcification and osteoblast phenotype differentiation induced by IL-18.Conclusions: These findings suggest that obesity-related inflammation induced by high-fat diet could exacerbate VC in CRF rats. Furthermore, serum IL-18 level had a positive correlation with the degree of VC. It is also found that IL-18 promoted osteogenic differentiation and calcification of rat VSMCs via p38 pathway activation.

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The Pharmacological Effect and Mechanism of Lanthanum Hydroxide on Vascular Calcification Caused by Chronic Renal Failure Hyperphosphatemia

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.639127 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lulu Zhao ◽

Shengnan Wang ◽

Hong Liu ◽

Xiaoli Du ◽

Ren Bu ◽

...

Keyword(s):

Signal Transduction ◽

Renal Failure ◽

Chronic Renal Failure ◽

Vascular Calcification ◽

Signal Transduction Pathway ◽

Calcium Content ◽

Normal Diet ◽

Lanthanum Hydroxide ◽

Serum Biochemical

ObjectiveThe present work aimed to explore the efficacy of lanthanum hydroxide in managing the vascular calcification induced by hyperphosphate in chronic renal failure (CRF) as well as the underlying mechanism.MethodsRats were randomly allocated to five groups: normal diet control, CKD hyperphosphatemia model, CKD model treated with lanthanum hydroxide, CKD model receiving lanthanum carbonate treatment, together with CKD model receiving calcium carbonate treatment. The serum biochemical and kidney histopathological parameters were analyzed. The aortic vessels were subjected to Von Kossa staining, CT scan and proteomic analysis. In vitro, the calcium content and ALP activity were measured, and RT-PCR (SM22α, Runx2, BMP-2, and TRAF6) and Western blot (SM22α, Runx2, BMP-2, TRAF6, and NF-κB) were performed.ResultsIn the lanthanum hydroxide group, serum biochemical and kidney histopathological parameters were significantly improved compared with the model group, indicating the efficacy of lanthanum hydroxide in postponing CRF progression and in protecting renal function. In addition, applying lanthanum hydroxide postponed hyperphosphatemia-mediated vascular calcification in CKD. Furthermore, lanthanum hydroxide was found to mitigate vascular calcification via the NF-κB signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl3) alleviated phosphate-mediated calcification and suppressed the activation of NF-κB as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-κB, BMP-2, Runx2, and TRAF6 expression.ConclusionLanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.

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Diet therapy on hypertriglyceridemia in patients with chronic renal failure. Part 1. Effect of low-carbohydrate and high-fat diet.

The Japanese Journal of Nutrition and Dietetics ◽

10.5264/eiyogakuzashi.43.27 ◽

1985 ◽

Vol 43 (1) ◽

pp. 27-33

Author(s):

Tomiko Yoneda ◽

Tamako Noguchi ◽

Yoshiko Kii ◽

Yusuke Tsukamoto ◽

Michihito Okubo ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

High Fat Diet ◽

Diet Therapy ◽

High Fat ◽

Low Carbohydrate

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MiR-93 inhibits the vascular calcification of chronic renal failure by suppression of Wnt/β-catenin pathway

International Urology and Nephrology ◽

10.1007/s11255-021-02907-6 ◽

2021 ◽

Author(s):

Jun Peng ◽

Chao Qin ◽

Shu-Yan Tian ◽

Jia-Qing Peng

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Vascular Calcification

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Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000374037 ◽

2015 ◽

Vol 35 (6) ◽

pp. 2349-2359 ◽

Cited By ~ 42

Author(s):

Youli Xi ◽

Miaozong Wu ◽

Hongxia Li ◽

Siqi Dong ◽

Erfei Luo ◽

...

Keyword(s):

Protein Kinase ◽

Fatty Liver ◽

High Fat Diet ◽

Molecular Mechanisms ◽

Liver Steatosis ◽

Serum Levels ◽

Whole Body ◽

Therapeutic Effects ◽

High Fat ◽

Dependent Protein

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

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FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice

ACTA MEDICA IRANICA ◽

10.18502/acta.v60i1.8326 ◽

2022 ◽

Author(s):

Somayeh Aslani ◽

Saman Bahrambeigi ◽

Davoud Sanajou

Keyword(s):

Liver Injury ◽

High Fat Diet ◽

Lifestyle Modification ◽

Serum Levels ◽

Diabetic Mice ◽

High Fat ◽

Lifestyle Modifications ◽

Gamma Glutamyl Transpeptidase ◽

Alcoholic Fatty Liver

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.

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Magnesium Citrate Protects Against Vascular Calcification in an Adenine-induced Chronic Renal Failure Rat Model

Journal of Cardiovascular Pharmacology ◽

10.1097/fjc.0000000000000590 ◽

2018 ◽

Vol 72 (6) ◽

pp. 270-276 ◽

Cited By ~ 2

Author(s):

Zhihui Yao ◽

Yang Xu ◽

Weidong Ma ◽

Xin-Yuan Sun ◽

Shan Jia ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Vascular Calcification ◽

Rat Model ◽

Magnesium Citrate

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P1244MILD DIFFERENCES IN CARDIAC CALCIFICATION BETWEEN WILD TYPE AND SCLEROSTIN KNOCKOUT MICE WITH CKD

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1244 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Annelies De Maré ◽

Patrick D'Haese ◽

Anja Verhulst

Keyword(s):

Renal Failure ◽

Soft Tissue ◽

Bone Formation ◽

Serum Creatinine ◽

Calcium Content ◽

Serum Levels ◽

Ectopic Calcification ◽

Wild Type ◽

Protective Function ◽

Flame Atomic Absorption

Abstract Background and Aims Ectopic soft tissue calcifications, especially cardiovascular calcifications, are frequently observed in patients with chronic kidney disease (CKD) and are associated with increased morbidity and mortality. Sclerostin, a well-known inhibitor of bone formation, shows significantly increased serum levels in CKD patients. Since the process of ectopic calcification shares many similarities with physiological bone formation, we investigated a possible role for sclerostin in ectopic calcification development. Method CKD was induced in wild type (WT) (n=21) and sclerostin knockout (Sost ko) mice (n = 21), both on a C57Bl6/J background, by the alternate administration of a 0.30% and 0.15% adenine supplemented diet, containing 1% phosphate. A normal renal function control group receiving standard mouse chow (WT C57Bl6/J n = 8) was also included in the study. Serum creatinine and phosphate levels were measured at the start and end of the study to assess CKD development. At sacrifice, the calcium content of the kidneys, heart and aorta was determined by flame atomic absorption spectrometry. Results The adenine-supplemented diet led to a clear induction of CKD in both the Sost ko and wild type mice, as reflected by increased serum creatinine (0.38 ± 0.09 mg/dL in control mice vs 0.65 ± 0.18 mg/dL in adenine-exposed mice, p<0.0001) and phosphate levels (9.12 ± 1.16 mg/dL in control mice vs 19.03 ± 3.11 mg/dL in adenine-exposed mice, p<0.0001). The Sost ko and WT mice receiving the adenine diet, developed the same degree of renal failure, since there were no differences in serum levels of creatinine (p=0.0507) and phosphate (p=0.4890). Significantly higher amounts of calcium were measured in the kidney (0.05 ± 0.01 mg/g wet tissue vs 3.70 ± 2.00 mg/g wet tissue, p<0.0001) and the heart (0.03 ± 0.01 mg/g wet tissue vs 0.07 ± 0.04 mg/g wet tissue, p<0.0001) of adenine-exposed mice, compared to mice receiving the control diet. Furthermore, Sost ko mice had a significantly higher calcium content in the heart compared to the WT mice with renal failure (0.05 ± 0.03 mg/g wet tissue in WT mice vs 0.08 ± 0.05 mg/g wet tissue in Sost ko mice, p = 0.0029). No differences were observed in aortic calcium content between control mice and mice with renal failure. Conclusion In this study we managed to develop a mouse model of CKD-induced soft tissue calcification in the heart and kidneys of the animals, however no calcifications developed in the aorta. The higher calcium content that was observed in the heart of Sost ko mice compared to WT mice, might be an indication of a protective function of sclerostin during ectopic cardiac calcification

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Tumor Markers in Patients with Chronic Renal Failure

The International Journal of Biological Markers ◽

10.1177/172460089000500207 ◽

1990 ◽

Vol 5 (2) ◽

pp. 85-88 ◽

Cited By ~ 39

Author(s):

X. Filella ◽

A. Cases ◽

R. Molina ◽

J. Jo ◽

J.L. Bedini ◽

...

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Tumor Markers ◽

Specific Antigen ◽

Neuron Specific Enolase ◽

Serum Levels ◽

Carbohydrate Antigen ◽

Ca 125 ◽

Renal Metabolism ◽

Ca 50

In order to evaluate the specificity of tumor markers in chronic renal failure, we have determined serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), carbohydrate antigen 50 (CA 50), alfafetoprotein (AFP), neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), squamous cell carcinoma antigen (SCC), carbohydrate antigen 15.3 (CA 15.3) and carbohydrate antigen 125 (CA 125) in 30 patients with cronic renal failure and in 36 hemodialyzed patients without clinical evidence of neoplasia. CEA, CA 50, NSE and SCC frequently show increased serum levels, suggesting a renal metabolism, while others remain, generally, within the normal levels.

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Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE−/− Mice

BioMed Research International ◽

10.1155/2019/7157865 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Huadong Liu ◽

Wei Xiong ◽

Yu Luo ◽

Hua Chen ◽

Yaqiong He ◽

...

Keyword(s):

P38 Mapk ◽

High Fat Diet ◽

Transforming Growth Factor ◽

Elevated Serum ◽

Serum Levels ◽

Nuclear Antigen ◽

High Fat ◽

Aortic Plaque ◽

Protein Levels ◽

Progression Of Atherosclerosis

Background. Vascular remodeling is the most critical pathogenesis of atherosclerosis. Adipokine chemerin was known for its relationship with obesity as well as metabolism. Most recently, chemerin was found to play a crucial role in the pathologic process of cardiovascular diseases including coronary heart disease. In this study, we surveyed the role of chemerin in progression of atherosclerosis in ApoE−/− mice. Objective. To investigate the relationship between chemerin and progression of atherosclerosis in ApoE−/− mice and its mechanism. Methods. 8-week-old ApoE−/− mice were fed with high-fat diet to induce the atherosclerosis model. Adenoviruses were transfected for knockdown or overexpression of chemerin gene into aorta. Serums and aortic tissues of ApoE−/− mice were obtained after feeding high-fat diet for 16 weeks. HE staining and oil red staining were performed to evaluate aortic plaque. ELISA was performed to explore serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β1 (TGF-β1). Real-time PCR and western blotting were carried out to investigate the mRNA and protein levels of chemerin, nuclear factor-κB p65 (NF-κBp65), proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK 1/2). Result. Aortic plaque formation was significantly induced by high-fat diet in ApoE−/− mice. Simultaneously, elevated serum levels of TNF-α and IL-1β and elevated mRNA and protein levels of chemerin, NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 were found in ApoE−/− mice. After aortic chemerin gene was inhibited by adenovirus, aortic atherosclerosis induced by high-fat diet was significantly meliorated, serum levels of TNF-α and IL-1β decreased, mRNA and protein levels of NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 decreased simultaneously. Conclusion. Our study revealed that chemerin stimulated the progression of atherosclerosis in ApoE−/− mice.

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