Abstract 288: Atheroprotective Effect of Probucol Is Related to Its Heme Oxygenase 1 Activation and Subsequent Suppression of Oxidized Low-Density Lipoprotein--Induced Dendritic Cell Maturation

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aijun Sun ◽  
Xueting Jin ◽  
Jingjing Zhao ◽  
Keqiang Wang ◽  
Fang Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Heme Oxygenase ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
High Fat ◽  
Atherosclerotic Lesions

Aims: Probucol, an agent characterized by lipid-lowering and anti-oxidant property, retards atherosclerosis effectively. Our study aimed to test the hypothesis that probucol might act its anti-athersclerotic role by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). Furthermore, we also used a LDLR-/- mice model fed a high-fat diet to detect whether probucol also perform its anti-atherosclerotic effect on suppressing DCs maturation in vivo. Methods: H-monDCs were derived by incubating purified human monocytes with GM-CSF and IL-4. H-monDCs were pre-incubated with or without probucol and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of heme oxygenase (HO-1) siRNA. In vivo studies, streptozotocin (STZ) induced LDLR-/- mice were fed either a high-fat (HF) diet or added with 0.5% probucol for 4 months. Expression of h-monDC membrane molecules and mice splenic CD11c+DC membrane molecules were analyzed by FACS, cytokines were measured by ELISA and the STAT1/CIITA associated signaling pathway was determined by Western blotting. Mice aortic lesions were observed by En face staining and the expression of CD11c+DCs within atherosclerotic plaques were shown under confocal microscopy. Results: Ox-LDL promoted h-monDC maturation and TNF-a production; and up-regulated STAT1 701 phosphorylation by activating HO-1 in STAT1/CIITA signaling pathway. These effects were inhibited by probucol. Knocking down HO-1 with specific siRNA blocked these effects of probucol. In LDLR-/- mice fed a high-fat diet, probucol treatment significantly regressed aortic atherosclerotic lesions, suppressed splenic CD11c+DCs maturation and IL-12p70 production; and resulted in absence of CD11c+DCs within atherosclerotic lesions. Conclusions: Our study indicated that probucol effectively suppressed maturation of h-monDC induced by ox-LDL through HO-1 activation, and retarded atherosclerosis at least partly through inhibiting maturations of CD11c+DCs in LDLR-/- mice.

scholarly journals Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Liang Liu ◽  
Chao Gao ◽  
Ping Yao ◽  
Zhiyong Gong
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Mrna And Protein Expression ◽  
Ldl Uptake ◽  
Underlying Mechanisms

A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved.

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 The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats

2021 ◽  
Author(s):  
Maria Donatella Semeraro ◽  
Gunter Almer ◽  
Melanie Kaiser ◽  
Sieglinde Zelzer ◽  
Andreas Meinitzer ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Serum Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
High Fat ◽  
Nitric Oxide Metabolites

Abstract Purpose Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.

scholarly journals Kiwifruit Supplementation Increases the Activity of the Paraoxonase Enzyme and decreases Oxidized Low-Density Lipoprotein in High-Fat Diet Fed Hamsters

2020 ◽  
Vol 8 (2) ◽  
pp. 58-63
Author(s):  
Narjes Rezaei ◽  
Zahra Zaherijamil ◽  
Shirin Moradkhani ◽  
Massoud Saidijam ◽  
Iraj khodadadi ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Normal Diet ◽  
Paraoxonase 1 ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
High Fat ◽  
Beneficial Effects ◽  
The Impact

Background: It is shown that kiwifruit elevates serum high-density lipoprotein cholesterol (HDL-C) levels and exhibits beneficial effects on human health due to its antioxidant potential. Objectives: This study aimed to investigate the impact of kiwifruit on the activity of the paraoxonase 1 (PON1) enzyme, as a main antioxidant enzyme in HDL functionality, in a high-fat diet (HFD). Methods: To this end, 42 male Syrian hamsters were divided into 6 groups including hamsters receiving a normal diet (the control normal group), a regular diet supplemented with kiwifruit at two concentrations (i.e., 1.86 g/kg and 3.73 g/kg), a HFD comprised of 15% butterfat + 0.05% cholesterol (the control high-fat group), and a HFD supplemented with kiwifruit at two concentrations (i.e., 1.86 and 3.73 g/kg) for 8 weeks. Results: The results showed that supplementation of kiwifruit to the HFD increased the levels of HDL-C and remarkably reduced the concentrations of oxidized low-density lipoprotein (ox-LDL) and malondialdehyde (MDA) compared with the control-HF group. In addition, the paraoxonase activity of PON1 significantly increased in HFD supplemented with kiwifruit (1.86 g/kg), and finally, arylesterase (ARE) activity increased in all treated groups when compared with untreated groups. Conclusion: Our findings suggested that kiwifruit can improve the lipid profile and prevent oxidative stress-induced by lipid peroxidation in hamsters receiving HFD, thus increasing the ARE and paraoxonase activities of PON1.

scholarly journals Pdcd4 Is Involved in the Formation of Stress Granule in Response to Oxidized Low-Density Lipoprotein or High-Fat Diet

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159568 ◽  
Author(s):  
Yang Bai ◽  
Zhaojing Dong ◽  
Qianwen Shang ◽  
Hui Zhao ◽  
Liyang Wang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Stress Granule ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
High Fat

Abstract 1454: Targeted Molecular Imaging Probes For In Vivo MR Detection Of Atherosclerotic Lesions Using Antibodies Against Oxidized Low Density Lipoprotein

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Karen C Briley-Saebo ◽  
Willem Mulder ◽  
Peter X Shaw ◽  
Seung-Hyuk Choi ◽  
Venkatesh Mani ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Mr Imaging ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Atherosclerotic Lesions ◽  
Molecular Imaging Probes ◽  
Imaging Probes

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the initiation, progression and destabilization of atherosclerotic plaque. Molecular imaging probes that target OxLDL may allow in vivo detection of vulnerable plaques. In this study, magnetic resonance imaging (MRI) was used to detect atherosclerotic lesions in apolipoprotein deficient mice (ApoE−/−) using micelles comprised of gadolinium lipids, fluorescent rhodamine, PEG-lipids, and MDA2, a murine monoclonal antibody that binds malondialdehyde (MDA) lysine epitopes present in OxLDL. Materials and Results: Untargeted micelles, MDA2-labeled micelles and nonspecific polyclonal IgG micelles were prepared and characterized with respect to OxLDL binding capacity, pharmacokinetics, and biodistribution in wild type (WT) and ApoE−/− mice. MR imaging was performed at 9.4T over a 3-week interval after administration of 0.075 mmol Gd/kg micelles. MDA2 increased the micelle size, blood half-life, and MR efficacy relative to untargeted and IgG-micelles. Maximal plaque enhancement (>125%) was observed 72 hours post MDA2-micelle injection (Figure ). Untargeted and IgG-micelles did not exhibit significant wall enhancement at any of the time points studied. Confocal microscopy revealed that MDA2-micelles accumulate within foam cells associated with atherosclerotic plaque. WT mice showed no significant MR wall enhancement for any of the micelles studied. Conclusions: MR imaging using MDA2-micelles demonstrates specific targeting of OxLDL and foam cells and provides excellent MR image quality. This study suggests that it may be feasible to image similar atherosclerotic lesions in humans with MRI.

scholarly journals Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

1994 ◽  
Vol 35 (4) ◽  
pp. 669-677
Author(s):  
H.N. Hodis ◽  
D.M. Kramsch ◽  
P. Avogaro ◽  
G. Bittolo-Bon ◽  
G. Cazzolato ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein
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