scholarly journals CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice

2017 ◽  
Vol 114 (2) ◽  
pp. 312-323 ◽  
Author(s):  
Sebastian Steven ◽  
Mobin Dib ◽  
Michael Hausding ◽  
Fatemeh Kashani ◽  
Matthias Oelze ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Immune Cell ◽  
Vascular Inflammation ◽  
Human Study ◽  
Isometric Tension ◽  
Wild Type ◽  
High Fat ◽  
Aorta Ascendens

Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery. Conclusion CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease.

P6285Protective effects of exercise on vascular function are mediated by NADPH oxidase 4

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Morawietz ◽  
H Langbein ◽  
A Shahid ◽  
A Hofmann ◽  
J Mittag ◽  
...  
Keyword(s):  
Physical Activity ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Intracellular Calcium ◽  
High Fat Diet ◽  
Calcium Release ◽  
Protective Effects ◽  
Wild Type ◽  
High Fat ◽  
Exercise Induced

Abstract Background/Introduction Physical activity is one of the most potent strategies to prevent endothelial dysfunction. Recent evidence indicates vaso-protective properties of H2O2 produced by main endothelial NADPH oxidase isoform 4 (Nox4) in the vasculature. Purpose Therefore, we hypothesized that Nox4 connects physical activity with vaso-protective effects. Methods and results Analysis of endothelial function by Mulvany myograph showed endothelial dysfunction in wild-type as well as in Nox4−/− mice after 20 weeks on high-fat diet. Access to voluntary running wheels during high-fat diet prevented endothelial dysfunction in wild-type but not in Nox4−/− mice. Mechanistically, exercise led to increased H2O2 release in the aorta of wild-type mice with increased phosphorylation of eNOS pathway member AKT serine/threonine kinase 1 (Akt1), subsequently. Both effects were diminished in aortas of Nox4−/− mice. Deletion of Nox4 also led to decreased capacity for intracellular calcium release and reduced phenylephrine-mediated contraction, whereas potassium-induced contraction was unaffected. H2O2 scavenger catalase reduced phenylephrine-contraction in wild-type mice. Supplementation of H2O2 increased phenylephrine-induced contraction in Nox4−/− mice. Exercise induced key regulator of mitochondria biogenesis peroxisome proliferative activated receptor gamma, coactivator 1 alpha (Ppargc1a) in wild-type but not Nox4−/− mice. Furthermore, exercise induced citrate synthase activity and reduced mitochondria mass in the absence of Nox4. Thus, Nox4−/− mice became less active and ran less compared with wild-type mice. Conclusions Nox4 derived H2O2 plays a key role in exercise-induced adaptations of eNOS and Ppargc1a pathway and intracellular calcium release. Hence, loss of Nox4 diminished physical activity performance and vascular protective effects of exercise. Acknowledgement/Funding This work was supported by a research grant of the German Cardiac Society (DGK) (to H.L.) and DFG (Grant MO 1695/4-1 to H.M.).

scholarly journals Simvastatin and tempol protect against endothelial dysfunction and renal injury in a model of obesity and hypertension

2010 ◽  
Vol 298 (1) ◽  
pp. F86-F94 ◽  
Author(s):  
Sarah F. Knight ◽  
Jianghe Yuan ◽  
Siddhartha Roy ◽  
John D. Imig
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Renal Injury ◽  
High Fat Diet ◽  
Glomerular Injury ◽  
High Fat ◽  
Simvastatin Treatment ◽  
Wky Rats ◽  
Wistar Kyoto

Obesity and hypertension are risk factors for the development of chronic kidney disease. The mechanisms by which elevated blood pressure and fatty acids lead to the development of renal injury are incompletely understood. Here, we investigated the contributions of cholesterol and oxidative stress to renal endothelial dysfunction and glomerular injury in a model of obesity and hypertension. Male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were fed a normal diet, a high-fat diet, a high-fat diet with tempol, or a high-fat diet with simvastatin for up to 10 wk. Blood pressure was not altered by a high-fat diet or treatments. After 3 wk, renal afferent dilatory responses to acetylcholine were impaired in WKY rats and SHR fed a high-fat diet. Tempol treatment prevented this vascular dysfunction in both strains; however, simvastatin treatment demonstrated greater beneficial effects in the SHR. Albuminuria was observed in the SHR and was exacerbated by a high-fat diet. Tempol and simvastatin treatment significantly ameliorated albuminuria in the SHR fed a high-fat diet. Ten weeks on a high-fat resulted in an increase in urinary 8-isoprostane in WKY rats and SHR, and tempol and simvastatin treatment prevented this increase, indicating a reduction in renal oxidative stress. Monocyte chemoattractant protein-1 (MCP-1) excretion was significantly elevated by a high-fat diet in both strains, and tempol prevented this increase. Interestingly, simvastatin treatment had no effect on MCP-1 levels. These data indicate that tempol and simvastatin treatment via a reduction in oxidative stress improve renal endothelial function and decrease glomerular injury in a model of obesity and hypertension.

scholarly journals From the Cover: Zinc Deficiency Worsens and Supplementation Prevents High-Fat Diet Induced Vascular Inflammation, Oxidative Stress, and Pathological Remodeling

2016 ◽  
Vol 153 (1) ◽  
pp. 124-136 ◽  
Author(s):  
Jun Chen ◽  
Shudong Wang ◽  
Manyu Luo ◽  
Zhiguo Zhang ◽  
Xiaozhen Dai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Zinc Deficiency ◽  
High Fat Diet ◽  
Vascular Inflammation ◽  
High Fat ◽  
Pathological Remodeling

Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice

2010 ◽  
Vol 28 (10) ◽  
pp. 2111-2119 ◽  
Author(s):  
Renata Kobayasi ◽  
Eliana H Akamine ◽  
Ana P Davel ◽  
Maria AM Rodrigues ◽  
Carla RO Carvalho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Inflammatory Mediators ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Obesity In Mice

scholarly journals Effect of Vinyl Chloride Exposure on Cardiometabolic Toxicity

2021 ◽  
Author(s):  
Igor N Zelko ◽  
Breandon S Taylor ◽  
Trinath P Das ◽  
Walter H Watson ◽  
Israel D Sithu ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Vinyl Chloride ◽  
High Fat Diet ◽  
Low Dose ◽  
Immune Cell ◽  
Vascular Inflammation ◽  
Pulmonary Inflammation ◽  
Ldl Receptor ◽  
Consumer Products ◽  
High Fat

Vinyl chloride is an organochlorine mainly used to manufacture its polymer polyvinyl chloride, which is extensively used in the manufacturing of consumer products. Recent studies suggest that chronic low dose vinyl chloride exposure affects glucose homeostasis in high fat diet-fed mice. Our data suggest that even in the absence of high fat diet, exposure to vinyl chloride (0.8 ppm, 6h/day, 5day/week, for 12 weeks) induces glucose intolerance (1.0 g/kg, i.p) in male C57BL/6 mice. This was accompanied with the depletion of hepatic glutathione and a modest increase in lung interstitial macrophages. Vinyl chloride exposure did not affect the levels of circulating immune cells, endothelial progenitor cells, platelet-immune cell aggregates, and cytokines and chemokines. The acute challenge of vinyl chloride-exposed mice with LPS did not affect lung immune cell composition or plasma IL-6. To examine the effect of vinyl chloride exposure on vascular inflammation and atherosclerosis, LDL receptor-KO mice on C57BL/6 background maintained on western diet were exposed to vinyl chloride for 12 weeks (0.8 ppm, 6h/day, 5day/week). Unlike the WT C57BL/6 mice, vinyl chloride exposure did not affect glucose tolerance in the LDL receptor-KO mice. Plasma cytokines, lesion area in the aortic valve, and markers of lesional inflammation in vinyl chloride-exposed LDL receptor-KO mice were comparable with the air-exposed controls. Collectively, despite impaired glucose tolerance and modest pulmonary inflammation, chronic low dose vinyl chloride exposure does not affect surrogate markers of cardiovascular injury, LPS-induced acute inflammation in C57BL/6 mice, and chronic inflammation and atherosclerosis in the LDL receptor-KO mice.

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