Abstract P199: Uric Acid Promotes Vascular Stiffness, Immune Inflammatory Response and Proteinuria in Western Diet Fed Mice

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Annayya Aroor ◽  
Guanghong Jia ◽  
Vincent G DeMarco ◽  
Javad Habibi ◽  
Zhe Sun ◽  
...  
Keyword(s):  
Uric Acid ◽  
Inflammatory Response ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Western Diet ◽  
Vascular Stiffness ◽  
Aortic Endothelial Cells ◽  
Force Microscopy ◽  
Atomic Force ◽  
High Fructose

Increased consumption of a diet high in fructose and fat (western diet, WD) is associated with an increase in cardiovascular disease (CVD) and kidney injury. In this regard, excess hepatic production of uric acid generated from excess fructose consumption is emerging as a risk factor for vascular stiffness, which underpins CVD and kidney injury. We hypothesized that a WD would increase uric acid levels and cardiovascular and renal xanthine oxidase (XO) activity and associated increased vascular stiffness and proteinuria. Furthermore, we proposed that inhibition of XO activity would prevent arterial stiffening and reduce proteinuria in a clinically relevant model of WD-induced CVD and renal injury. Four week-old C57BL6/J male mice were fed a WD containing high fat (46%), sucrose (17.5%), and high fructose corn syrup (17.5%) with or without allopurinol (125mg/L), a potent XO inhibitor for 16 weeks. XO inhibition significantly attenuated WD-induced increases in plasma and urine uric acid levels and aortic XO activity (WD, 0.225 + 0.031 mU/mL WD + allopurinol, 0.097+ 0.026mU/mL, P<0.05), as well as proteinuria (WD, 20.92 + 2.66 mg/ mg creatinine, WD + allopurinol, 13.48 + 1.56 mg/mg creatinine, P<0.05). XO inhibition had no effect on increases in body weight, fat mass, and HOMA-IR promoted by the WD. Blood pressure was not different between any of the groups. Stiffness of aortic endothelial cells, extracellular matrix and vascular smooth muscle cells, as determined by atomic force microscopy, was significantly increased in WD mice and this was prevented by XO inhibition. WD induced a significant macrophage pro-inflammatory response in aorta that was significantly suppressed by XO inhibition. Collectively, these findings support the notion that increased XO activity in the vasculature and kidney and increased hepatic production of uric acid secondary to consumption of a WD promotes vascular stiffness, vascular inflammation and a maladaptive immune response that lead to vascular stiffness and kidney injury.

scholarly journals Xanthine oxidase inhibition protects against Western diet-induced aortic stiffness and impaired vasorelaxation in female mice

2017 ◽  
Vol 313 (2) ◽  
pp. R67-R77 ◽  
Author(s):  
Guido Lastra ◽  
Camila Manrique ◽  
Guanghong Jia ◽  
Annayya R. Aroor ◽  
Melvin R. Hayden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Arterial Stiffness ◽  
Xanthine Oxidase ◽  
Aortic Stiffness ◽  
Plasma Concentrations ◽  
Western Diet ◽  
Vascular Stiffness ◽  
High Fructose ◽  
The Impact

Consumption of a high-fat, high-fructose diet [Western diet (WD)] promotes vascular stiffness, a critical factor in the development of cardiovascular disease (CVD). Obese and diabetic women exhibit greater arterial stiffness than men, which contributes to the increased incidence of CVD in these women. Furthermore, high-fructose diets result in elevated plasma concentrations of uric acid via xanthine oxidase (XO) activation, and uric acid elevation is also associated with increased vascular stiffness. However, the mechanisms by which increased xanthine oxidase activity and uric acid contribute to vascular stiffness in obese females remain to be fully uncovered. Accordingly, we examined the impact of XO inhibition on endothelial function and vascular stiffness in female C57BL/6J mice fed a WD or regular chow for 16 wk. WD feeding resulted in increased arterial stiffness, measured by atomic force microscopy in aortic explants (16.19 ± 1.72 vs. 5.21 ± 0.54 kPa, P < 0.05), as well as abnormal aortic endothelium-dependent and -independent vasorelaxation. XO inhibition with allopurinol (widely utilized in the clinical setting) substantially improved vascular relaxation and attenuated stiffness (16.9 ± 0.50 vs. 3.44 ± 0.50 kPa, P < 0.05) while simultaneously lowering serum uric acid levels (0.55 ± 0.98 vs. 0.21 ± 0.04 mg/dL, P < 0.05). In addition, allopurinol improved WD-induced markers of fibrosis and oxidative stress in aortic tissue, as analyzed by immunohistochemistry and transmission electronic microscopy. Collectively, these results demonstrate that XO inhibition protects against WD-induced vascular oxidative stress, fibrosis, impaired vasorelaxation, and aortic stiffness in females. Furthermore, excessive oxidative stress resulting from XO activation appears to play a key role in mediating vascular dysfunction induced by chronic exposure to WD consumption in females.

scholarly journals High-Fructose Diet Increases Inflammatory Cytokines and Alters Gut Microbiota Composition in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yong Wang ◽  
Wentao Qi ◽  
Ge Song ◽  
Shaojie Pang ◽  
Zhenzhen Peng ◽  
...  
Keyword(s):  
Uric Acid ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Lipid Accumulation ◽  
Fasting Blood Glucose ◽  
High Fructose Diet ◽  
Fructose Intake ◽  
High Fructose

High-fructose diet induced changes in gut microbiota structure and function, which have been linked to inflammatory response. However, the effect of small or appropriate doses of fructose on gut microbiota and inflammatory cytokines is not fully understood. Hence, the abundance changes of gut microbiota in fructose-treated Sprague-Dawley rats were analyzed by 16S rRNA sequencing. The effects of fructose diet on metabolic disorders were evaluated by blood biochemical parameter test, histological analysis, short-chain fatty acid (SCFA) analysis, ELISA analysis, and Western blot. Rats were intragastrically administered with pure fructose at the dose of 0 (Con), 2.6 (Fru-L), 5.3 (Fru-M), and 10.5 g/kg/day (Fru-H) for 20 weeks. The results showed that there were 36.5% increase of uric acid level in the Fru-H group when compared with the Con group. The serum proinflammatory cytokines (IL-6, TNF-α, and MIP-2) were significantly increased ( P < 0.05 ), and the anti-inflammatory cytokine IL-10 was significantly decreased ( P < 0.05 ) with fructose treatment. A higher fructose intake induced lipid accumulation in the liver and inflammatory cell infiltration in the pancreas and colon and increased the abundances of Lachnospira, Parasutterella, Marvinbryantia, and Blantia in colonic contents. Fructose intake increased the expressions of lipid accumulation proteins including perilipin-1, ADRP, and Tip-47 in the colon. Moreover, the higher level intake of fructose impaired intestinal barrier function due to the decrease of the expression of tight junction proteins (ZO-1 and occludin). In summary, there were no negative effects on body weight, fasting blood glucose, gut microbiota, and SCFAs in colonic contents of rats when fructose intake is in small or appropriate doses. High intake of fructose can increase uric acid, proinflammatory cytokines, intestinal permeability, and lipid accumulation in the liver and induce inflammatory response in the pancreas and colon.

Abstract 371: DPPIV Inhibitor MK0626 Prevents Western Diet Induced Renal Injury via Suppression of Kidney Tissue Ras

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ravi Nistala ◽  
Javad Habibi ◽  
Annayya Aroor ◽  
Melvin R Hayden ◽  
Mona Garro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Renal Injury ◽  
Sodium Excretion ◽  
The United States ◽  
Western Diet ◽  
Ang Ii ◽  
High Fructose ◽  
Dppiv Inhibitor ◽  
And Oxidative Stress

Objectives: Obesity is an independent risk factor for development and progression of renal injury. High fructose corn syrup consumption has coincided with the obesity epidemic in the United States. High fructose (60%) diets have been demonstrated to be associated with elevation in BP and worsening insulin resistance along with renal injury via increased hepatic production of uric acid. Recently, DPPIV inhibitors have been shown to improve diabetic changes and sodium excretion, effects that are beyond glycemic control. Therefore, the renal protective benefits of DPPIV inhibition in a clinically relevant Western diet fed mouse model were examined. Methods: Mice fed a high fat/high fructose (WD) diet for 16 weeks and given a DPPIV inhibitor MK0626 in their diet were examined for metabolic parameters, inflammation, kidney renin-angiotensin system (RAS) and oxidative stress. Renal injury was assessed by biochemical, immunohistological and electron microscopy techniques. In vitro , angiotensin II (Ang II) effects on OKP-PTCs were assessed for mechanism. Results: MK0626 ameliorated WD-induced increases in serum uric acid, oxidative stress and RAS. WD induced suppression of IL-10 was reversed by MK0626. There was a tendency to improve HOMA-IR by MK0626 but no effect on BP and body weights. Diet induced DPPIV activation in the plasma and kidney of WD mice was abrogated by MK0626 (~80%). WD mice were characterized by increased proteinuria (~3-fold), mesangial expansion and podocyte effacement and these changes were prevented by MK0626. In addition, the PTC endocytosis protein megalin and basilar canalicular network and mitochondrial ultrastructure abnormalities were reversed by MK0626. WD mice had decreased sodium excretion which was improved by MK0626. Ang II directly increased DPPIV activity and sodium hydrogen exchanger activity in PTCs and decreased megalin protein, which was effectively prevented by MK0626. Conclusion: Thus, WD induced increases in DPPIV activity is associated with elevations in uric acid, renal RAS, inflammation and oxidative stress which may result in renal injury. These results suggest that DPPIV inhibitors prevent WD induced renal injury and offer a novel therapy for diabetic and obesity associated renal disease.

scholarly journals Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice

Metabolism ◽  
2017 ◽  
Vol 74 ◽  
pp. 32-40 ◽  
Author(s):  
Annayya R. Aroor ◽  
Guanghong Jia ◽  
Javad Habibi ◽  
Zhe Sun ◽  
Francisco I. Ramirez-Perez ◽  
...  
Keyword(s):  
Uric Acid ◽  
Inflammatory Responses ◽  
Western Diet ◽  
Vascular Stiffness

scholarly journals A Comparison of Uric Acid Optical Detection Using as Sensitive Materials an Amino-Substituted Porphyrin and Its Nanomaterials with CuNPs, PtNPs and Pt@CuNPs

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 2072
Author(s):  
Camelia Epuran ◽  
Ion Fratilescu ◽  
Diana Anghel ◽  
Mihaela Birdeanu ◽  
Corina Orha ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Uric Acid ◽  
Copper Nanoparticles ◽  
Hybrid Material ◽  
Human Environment ◽  
Detection Range ◽  
Force Microscopy ◽  
Atomic Force ◽  
High Concentrations ◽  
Very High

Hybrid nanomaterials consisting in 5,10,15,20-tetrakis(4-amino-phenyl)-porphyrin (TAmPP) and copper nanoparticles (CuNPs), platinum nanoparticles (PtNPs), or both types (Pt@CuNPs) were obtained and tested for their capacity to optically detect uric acid from solutions. The introduction of diverse metal nanoparticles into the hybrid material proved their capacity to improve the detection range. The detection was monitored by using UV-Vis spectrophotometry, and differences between morphology of the materials were performed using atomic force microscopy (AFM). The hybrid material formed between porphyrin and PtNPs hasthe best and most stable response for uric acid detection in the range of 6.1958 × 10−6–1.5763 × 10−5 M, even in the presence of very high concentrations of the interference species present in human environment.

scholarly journals Inflammatory Response and Oxidative Stress as Mechanism of Reducing Hyperuricemia of Gardenia jasminoides-Poria cocos with Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lijun Liu ◽  
Shengjun Jiang ◽  
Xuqiang Liu ◽  
Qi Tang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Animal Experiments ◽  
Kidney Injury ◽  
Network Pharmacology ◽  
Poria Cocos ◽  
Gardenia Jasminoides ◽  
And Oxidative Stress

Hyperuricemia (HUA) is a metabolic disease, closely related to oxidative stress and inflammatory responses, caused by reduced excretion or increased production of uric acid. However, the existing therapeutic drugs have many side effects. It is imperative to find a drug or an alternative medicine to effectively control HUA. It was reported that Gardenia jasminoides and Poria cocos could reduce the level of uric acid in hyperuricemic rats through the inhibition of xanthine oxidase (XOD) activity. But there were few studies on its mechanism. Therefore, the effective ingredients in G. jasminoides and P. cocoa extracts (GPE), the active target sites, and the further potential mechanisms were studied by LC-/MS/MS, molecular docking, and network pharmacology, combined with the validation of animal experiments. These results proved that GPE could significantly improve HUA induced by potassium oxazine with the characteristics of multicomponent, multitarget, and multichannel overall regulation. In general, GPE could reduce the level of uric acid and alleviate liver and kidney injury caused by inflammatory response and oxidative stress. The mechanism might be related to the TNF-α and IL-7 signaling pathway.

Non-Hertzian Approach to Analyzing Mechanical Properties of Endothelial Cells Probed by Atomic Force Microscopy

2005 ◽  
Vol 128 (2) ◽  
pp. 176-184 ◽  
Author(s):  
Kevin D. Costa ◽  
Alan J. Sim ◽  
Frank C-P. Yin
Keyword(s):  
Atomic Force Microscopy ◽  
Endothelial Cells ◽  
Stress Fibers ◽  
Linear Structures ◽  
Mechanical Environment ◽  
Aortic Endothelial Cells ◽  
Force Microscopy ◽  
Linear Elastic ◽  
Apparent Modulus ◽  
Atomic Force

Detailed measurements of cell material properties are required for understanding how cells respond to their mechanical environment. Atomic force microscopy (AFM) is an increasingly popular measurement technique that uniquely combines subcellular mechanical testing with high-resolution imaging. However, the standard method of analyzing AFM indentation data is based on a simplified “Hertz” theory that requires unrealistic assumptions about cell indentation experiments. The objective of this study was to utilize an alternative “pointwise modulus” approach, that relaxes several of these assumptions, to examine subcellular mechanics of cultured human aortic endothelial cells (HAECs). Data from indentations in 2‐to5‐μm square regions of cytoplasm reveal at least two mechanically distinct populations of cellular material. Indentations colocalized with prominent linear structures in AFM images exhibited depth-dependent variation of the apparent pointwise elastic modulus that was not observed at adjacent locations devoid of such structures. The average pointwise modulus at an arbitrary indentation depth of 200nm was 5.6±3.5kPa and 1.5±0.76kPa (mean±SD, n=7) for these two material populations, respectively. The linear structures in AFM images were identified by fluorescence microscopy as bundles of f-actin, or stress fibers. After treatment with 4μM cytochalasin B, HAECs behaved like a homogeneous linear elastic material with an apparent modulus of 0.89±0.46kPa. These findings reveal complex mechanical behavior specifically associated with actin stress fibers that is not accurately described using the standard Hertz analysis, and may impact how HAECs interact with their mechanical environment.

scholarly journals Effects of Sporisorium Reiliana Polysaccharides and Phoenix Dactylifera Monosaccharides on the Gut Microbiota and Serum Metabolism in Mice with Fructose-Induced Hyperuricaemia

2021 ◽  
Author(s):  
Zhixuan Zhang ◽  
Ziyan Wang ◽  
Chenyang Lu ◽  
Jun Zhou ◽  
Jiaojiao Han ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gut Microbiota ◽  
Kidney Injury ◽  
Phoenix Dactylifera ◽  
Purine Metabolism ◽  
Bile Acid Metabolism ◽  
Serum Metabolites ◽  
Expression Of Genes ◽  
High Fructose ◽  
Sporisorium Reiliana

Abstract In recent decades, the prevalence of hyperuricaemia has increased, and dietary fructose is an important risk factor for the development of this disease. This study investigated and compared the effects of Sphacelotheca reiliana polysaccharides and Phoenix dactylifera monosaccharides on a series of physiological and biochemical indicators and on metagenomes and serum metabolites in mice with hyperuricaemia caused by a high-fructose diet. S. reiliana polysaccharides inhibited uric acid biosynthesis and promoted uric acid excretion, thereby alleviating the hyperuricaemia phenotype. In addition, hyperuricaemia was closely related to the gut microbiota. After treatment with S. reiliana polysaccharides, the abundance of Bacteroidetes and Proteobacteria in the mouse intestines was decreased, the expression of genes involved in glycolysis/gluconeogenesis metabolic pathways and purine metabolism was downregulated, and the dysfunction of the gut microbiota was alleviated. With regard to serum metabolism, the abundance of hippuric acid, uridine, kynurenic acid, propionic acid and arachidonoyl decreased, and the abundance of serum metabolites in inflammatory pathways involved in kidney injury and gout, such as bile acid metabolism, purine metabolism and tryptophan metabolism pathways, decreased. P. dactylifera monosaccharides aggravated hyperuricaemia. This research provides a valuable reference for the development of sugar applications.

Cryogenic atomic force microscopy

1991 ◽  
Vol 49 ◽  
pp. 54-55
Author(s):  
K. A. Fisher ◽  
M. G. L. Gustafsson ◽  
M. B. Shattuck ◽  
J. Clarke
Keyword(s):  
Room Temperature ◽  
Rapid Freezing ◽  
Cryogenic Temperatures ◽  
Soft Or ◽  
Electrically Conductive ◽  
Force Microscopy ◽  
Flexible Molecules ◽  
Advantages And Disadvantages ◽  
Atomic Force ◽  
Chemical Perturbation

The atomic force microscope (AFM) is capable of imaging electrically conductive and non-conductive surfaces at atomic resolution. When used to image biological samples, however, lateral resolution is often limited to nanometer levels, due primarily to AFM tip/sample interactions. Several approaches to immobilize and stabilize soft or flexible molecules for AFM have been examined, notably, tethering coating, and freezing. Although each approach has its advantages and disadvantages, rapid freezing techniques have the special advantage of avoiding chemical perturbation, and minimizing physical disruption of the sample. Scanning with an AFM at cryogenic temperatures has the potential to image frozen biomolecules at high resolution. We have constructed a force microscope capable of operating immersed in liquid n-pentane and have tested its performance at room temperature with carbon and metal-coated samples, and at 143° K with uncoated ferritin and purple membrane (PM).

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