scholarly journals Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet

2009 ◽  
Vol 8 (1) ◽  
pp. 30 ◽  
Author(s):  
Olena Sivak ◽  
Jerry Darlington ◽  
Pavel Gershkovich ◽  
Panayiotis P Constantinides ◽  
Kishor M Wasan
Keyword(s):  
Apolipoprotein E ◽  
High Fat Diet ◽  
Plasma Cholesterol ◽  
High Cholesterol ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

scholarly journals Effects of atorvastatin and/or probucol on recovery of atherosclerosis in high-fat-diet-fed apolipoprotein E–deficient mice

2019 ◽  
Vol 109 ◽  
pp. 1445-1453 ◽  
Author(s):  
Xiaokun Guo ◽  
Lin Wang ◽  
Xiaoshuang Xia ◽  
Peilu Wang ◽  
Xin Li
Keyword(s):  
Apolipoprotein E ◽  
High Fat Diet ◽  
High Fat ◽  
Deficient Mice

P4141Lack of IkBNS promotes cholate-containing high-fat diet-induced inflammation and atherogenesis in low-density lipoprotein (LDL) receptor-deficient mice

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Kitamura ◽  
K Isoda ◽  
K Akita ◽  
K Miyosawa ◽  
T Kadoguchi ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Aortic Root ◽  
High Fat Diet ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Endotoxin Shock ◽  
High Fat ◽  
Lps Challenge ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Abstract Background IκBNS is one of the nuclear IκB proteins and regulates a subset of Toll-like receptor (TLR) dependent genes. LPS acts as extremely strong stimulator of innate immunity. We tried to investigate whether stimulation of innate immunity could promote atherosclerosis in the IκBNS-deficient atherogenic mice. However all IκBNS-deficient mice died of LPS challenge at a dose of which almost all wild-type mice survived, because IκBNS-deficient mice are highly sensitive to LPS-induced endotoxin shock. Then, we decided to use a cholate-containing high fat diet (HFD(CA(+))), which has been widely used as an atherogenic diet in mice. Furthermore, HFD(CA(+)) has been shown to induce TLR4 mediated early inflammatory response. The present study aims to clarify the lack of IκBNS promotes atherogenesis in LDL receptor-deficient (LDLr−/−) mice fed HFD(CA(+)) compared with those fed a cholate-free HFD (HFD(CA(−)). Methods and results Mice that lacked IκBNS (IκBNS−/−) were crossed with LDLr−/− mice and formation of atherosclerotic lesions was analyzed after 6 weeks consumption of HFD(CA(+)) or HFD(CA(−)). The extent of atherosclerosis in the aorta (en face) was significantly increased in IκBNS−/−/LDLr−/−(CA(+)) mice compared with others after 6-week consumption of HFD (p<0.01) (Figure). Interestingly, HFD(CA(−)) did not induce significant atherosclerotic lesions in IκBNS−/−/LDLr−/− compared with LDLr−/− mice after 6-week consumption (Figure). Immunostaining of aortic root lesion revealed that HFD(CA(+)) significantly increased positive area of Mac-3 (macrophage) by 1.5-fold (p=0.01) and TLR4, interleukin-6 (IL-6) expression by 1.7-fold (P<0.05) and 1.5-fold (p<0.05) respectively in IκBNS−/−/LDLr−/− (CA(+)) compared to LDLr−/− (CA(+)) mice. Furthermore, active STAT3 (pSTAT3)-positive cells were significantly increased by 1.7-fold in the atherosclerotic lesions of IκBNS−/−/LDLr−/− (CA(+)) compared with LDLr−/− (CA(+)) mice (p<0.01). TLR4 positive areas, IL-6 positive areas, and pSTAT3 positive cells were overlapped with Mac-3, indicating that TLR4-IL-6-STAT3 axis was activated in macrophages in IκBNS−/−/LDLr−/− (CA(+)) mice. On the other hand, HFD(CA(−)) could not induce any difference in these immunoreactivities of arteriosclerotic lesions between IκBNS−/−/LDLr−/− (CA(−)) compared with LDLr−/− (CA(−)) mice. These findings suggest that IκBNS deficiency and HFD(CA(+)) promote atherogenesis in LDLr−/− mice via TLR4/IL-6/STAT3 pathway. Finally, we show the monocytes from peripheral blood of IκBNS−/−/LDLr−/− (CA(+)) mice were found to contain the most mounts of Ly6Chi among four groups, suggesting that lack of IκBNS enhances inflammation in the response HFD(CA(+)) feeding and thereby influence atherogenesis in IκBNS−/−/LDLr−/− mice. Aortic root atherosclerotic lesions Conclusions The present study is the first to demonstrate that the activation of innate immune system using HFD(CA(+)) induced significant inflammation and atherogenesis in IκBNS−/−/LDLr−/− compared with LDLr−/− mice.

scholarly journals Mobilization of sca1/flk-1 positive endothelial progenitor cells declines in apolipoprotein E-deficient mice with a high-fat diet

2015 ◽  
Vol 66 (6) ◽  
pp. 532-538 ◽  
Author(s):  
Martin Steinmetz ◽  
Eva Lucanus ◽  
Sebastian Zimmer ◽  
Georg Nickenig ◽  
Nikos Werner
Keyword(s):  
Apolipoprotein E ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
High Fat Diet ◽  
High Fat ◽  
Endothelial Progenitor ◽  
Deficient Mice

scholarly journals Cysteamine Decreases Low‐Density Lipoprotein Oxidation, Causes Regression of Atherosclerosis, and Improves Liver and Muscle Function in Low‐Density Lipoprotein Receptor–Deficient Mice

2021 ◽  
Vol 10 (18) ◽  
Author(s):  
Feroz Ahmad ◽  
Robert D. Mitchell ◽  
Tom Houben ◽  
Angela Palo ◽  
Tulasi Yadati ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Muscle Function ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Background We have shown previously that low‐density lipoprotein (LDL) can be oxidized in the lysosomes of macrophages, that this oxidation can be inhibited by cysteamine, an antioxidant that accumulates in lysosomes, and that this drug decreases atherosclerosis in LDL receptor–deficient mice fed a high‐fat diet. We have now performed a regression study with cysteamine, which is of more relevance to the treatment of human disease. Methods and Results LDL receptor–deficient mice were fed a high‐fat diet to induce atherosclerotic lesions. They were then reared on chow diet and drinking water containing cysteamine or plain drinking water. Aortic atherosclerosis was assessed, and samples of liver and skeletal muscle were analyzed. There was no regression of atherosclerosis in the control mice, but cysteamine caused regression of between 32% and 56% compared with the control group, depending on the site of the lesions. Cysteamine substantially increased markers of lesion stability, decreased ceroid, and greatly decreased oxidized phospholipids in the lesions. The liver lipid levels and expression of cluster of differentiation 68, acetyl–coenzyme A acetyltransferase 2, cytochromes P450 (CYP)27, and proinflammatory cytokines and chemokines were decreased by cysteamine. Skeletal muscle function and oxidative fibers were increased by cysteamine. There were no changes in the plasma total cholesterol, LDL cholesterol, high‐density lipoprotein cholesterol, or triacylglycerol concentrations attributable to cysteamine. Conclusions Inhibiting the lysosomal oxidation of LDL in atherosclerotic lesions by antioxidants targeted at lysosomes causes the regression of atherosclerosis and improves liver and muscle characteristics in mice and might be a promising novel therapy for atherosclerosis in patients.

scholarly journals Establishment of Type 2 Diabetes Mellitus Models Using High-Fat Diet and STZ in Bama Minipigs

2021 ◽  
Author(s):  
Yuqiong Zhao ◽  
Miaomiao Niu ◽  
Jia Yunxiao ◽  
Yuan Jifang ◽  
Xiang Lei ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
Normal Diet ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
High Cholesterol ◽  
High Fat ◽  
Accelerated Atherosclerosis ◽  
Atherosclerotic Lesions

Abstract BackgroundIn the past 20 years, the number of adults with diabetes has tripled. For most of the researches are often conducted in rodent T2DM models, and effective drugs developed have low clinical conversion efficiency. Therefore, it is urgent to establish a large animal model to explore the pathogenesis of T2DM and formulate disease prevention and control strategies. MethodsThis study was designed to establish and validate a T2DM model in minipigs with notable hyperglycemia using a high-fat diet and low-dose streptozotocin (STZ)，and examined the influence of STZ infusion time, the difference between a high-fat diet and a high-cholesterol and high-fat diet, and the atherosclerotic lesions accelerated by diabetes. Male Bama minipigs (n=24) were randomly divided into 5 groups; the control group was fed with normal diet for 9 months; STZ+HFD group and STZ+HCFD group were infused with 90 mg/kg STZ and then fed with a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively; HFD + STZ group and HCFD + STZ group were fed with a high-fat diet or high-cholesterol and high-fat diet, respectively, for nine months (after 3 months, pigs were injected with 90 mg/kg STZ intravenously). ResultsThe results showed the serum glucose concentrations were within the normal range in all groups except for HFD + STZ group and HCFD + STZ group. Animals fed with a high-fat diet for 9 months, did not develop apparent atherosclerotic lesions; nevertheless, atherosclerotic lesions were seen in animals fed with high-cholesterol and high-fat diets. Moreover, hyperglycemia accelerated atherosclerosis (lesions on the intimal surface of the abdominal aorta, 0.44±0.29 vs. 0.28±0.26) in minipigs. ConclusionsHigh-fat/high-cholesterol and high-fat diet combined with low-dose streptozotocin successfully established T2DM in minipigs. High-fat diet could not induce apparent atherosclerosis lesions but high-cholesterol and high-fat diet could during the nine months period. Hyperglycemia accelerated atherosclerosis in the minipigs.

Abstract 519: Endothelin-1-Induced Oxidative Stress and Inflammatory Cell Infiltration Play a Role in High-Fat Diet Induced-Atherosclerosis in Apolipoprotein E Knockout Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Melissa W Li ◽  
Pierre Paradis ◽  
Ernesto L Schiffrin
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Apolipoprotein E ◽  
High Fat Diet ◽  
Cell Infiltration ◽  
Ros Production ◽  
High Fat ◽  
T Cell Infiltration ◽  
Atherosclerotic Lesions ◽  
Perivascular Fat

Background: Endothelin (ET)-1 plays an important role in generation of reactive oxygen species (ROS) and inflammation in the vasculature. ET-1has been implicated in the pathogenesis of atherosclerosis since plasma and tissue ET-1 are increased in human and animal models of atherosclerosis. We observed that ET-1 overexpression exacerbates high-fat diet (HFD)-induced atherosclerosis in apolipoprotein E knockout ( apoE -/- ) mice. We hypothesized that ET-1-induced ROS and inflammation contribute to the development of atherosclerosis. Design and methods: Eight-week-old male transgenic mice overexpressing preproET-1 in the endothelium (eET-1), apoE -/- , eET-1/ apoE -/- and wild type mice were fed a HFD for 8 weeks. Aortic atherosclerotic lesions were quantified using Oil Red O staining. ROS production using dihydroethidium staining and monocyte/macrophage and T cell infiltration using immunofluorescence with MOMA-2 and anti-CD4 antibodies, respectively, were determined in perivascular fat, media and plaque in ascending aortic sections. Results: eET-1/ apoE -/- presented 3.8-fold more atherosclerotic lesions in whole aorta compared to apoE -/- ( P <0.01). ET-1 overexpression caused 2.6-, 1.9- and 1.9-fold increase in ROS production in perivascular fat, media and plaque of apoE -/- , respectively ( P <0.05). ET-1 overexpression increased monocyte/macrophage infiltration by 5- and 8-fold in perivascular fat and media, respectively ( P <0.05). CD4 + T cell infiltration was observed in perivascular fat and plaque of 3 and 5 of 6 eET-1/ apoE -/- compared to 0 and 1 of 6 apoE -/- , respectively ( P <0.05). Conclusions: These results suggest that ET-1 play an important role in progression of atherosclerotic lesions by increasing the oxidative stress and monocyte/macrophage and T cell infiltration in the atherosclerotic aorta, including the perivascular fat.

Abstract 347: Water-soluble Components of Sesame Oil Reduces Inflammation and Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Chandrakala Aluganti Narasimhulu ◽  
Krithika Selvarajan ◽  
Kathryn Burge ◽  
Dmitry Litvinov ◽  
Bhaswati Sengupta ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Plasma Lipids ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Sesame Oil ◽  
Water Soluble ◽  
Gene Analysis ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Anti Inflammatory

Background: Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Non-pharmacological means of treating chronic diseases have gained attention recently. We previously reported that the sesame oil aqueous extract (SOAE) has anti-inflammatory properties both in vitro and in vivo. In this study, we have determined whether SOAE has anti-atherosclerotic properties, and mechanisms by which it might modulate atherosclerosis by identifying genes and inflammatory markers. Methods and results: Low-density lipoprotein receptor knockout (LDLR-/-) female mice were fed with either high fat diet or high fat diet supplemented with SOAE. Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for global cytokine array. RNA was extracted from the liver tissue and the aorta and used for gene analysis. The SOAE-supplemented high fat diet significantly reduced atherosclerotic lesions, plasma cholesterol, and LDL cholesterol levels in LDLR-/- mice. Plasma inflammatory cytokines were reduced, but not significantly, demonstrating an anti-inflammatory property of SOAE. Gene analysis showed that SOAE-supplemented high fat diet reduced the genes involved in inflammation, and induced genes involved in cholesterol metabolism and reverse cholesterol transport. Conclusion: In conclusion, our studies suggest that a SOAE-enriched diet could be an effective non-pharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

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