scholarly journals IL-33 reduces the development of atherosclerosis

2008 ◽  
Vol 205 (2) ◽  
pp. 339-346 ◽  
Author(s):  
Ashley M. Miller ◽  
Damo Xu ◽  
Darren L. Asquith ◽  
Laura Denby ◽  
Yubin Li ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Chronic Inflammatory Disease ◽  
Total Serum ◽  
Atherosclerotic Plaques ◽  
Aortic Sinus ◽  
Serum Iga ◽  
Lymph Node Cells ◽  
Atherosclerosis Development

Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1–like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE−/− mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33–treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFNγ in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG1, but decreased IgG2a, which is consistent with a Th1-to-Th2 switch. IL-33–treated mice also produced significantly elevated antioxidized low-density lipoprotein (ox-LDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE−/− mice compared with control IgG-treated mice. Furthermore, coadministration of an anti–IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies.

scholarly journals Protective Effect of Vitamins C and E against Gasoline Vapors Induced Haematological and Biochemical Changes in Male Rats

2015 ◽  
Vol 7 (3) ◽  
pp. 139-149
Author(s):  
A. Sedky ◽  
H. Elsawy
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hemoglobin Concentration ◽  
Protective Role ◽  
Lipoprotein Cholesterol ◽  
Male Rats ◽  
Total Serum Protein ◽  
Total Serum ◽  
Control Group ◽  
Concomitant Treatment

The present work was designed to investigate the changes in some hematological, biochemical parameters and lipid profile as well as possible protective role of vitamins C and E against gasoline vapors induced toxicity in male rats. The present results showed that gasoline 80 vapors significantly decreased (p?0.05) the concentration of total serum protein (TSP) and albumin concentrations and increased (p?0.05) in serum activities of serum aminotransferases (ALT and AST) and alkaline phosphatase (ALP) compared to the control group. Also, exposure to gasoline 80 vapors induced significant decrease (p?0.05) in hemoglobin concentration, red blood cell count (RBCs), packed cell volume (PCV) and high density lipoprotein cholesterol (HDL-C) compared to control group. On the other hand, exposure to gasoline 80 vapors resulted in significant increase (p?0.05) in the levels of total cholesterol (TC), triglycerides (TGs), LDL-cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) relative to untreated experimental animals. However, concomitant treatment with gasoline vapors and administration of vitamins C and E exhibited a protective role on the observed toxic effect of gasoline vapors in male rats. The results of the present study indicated that toxic effects of gasoline vapors could be reduced by dietary supplementation of vitamins C and E.

scholarly journals Modulating Autoimmunity against LDL: Development of a Vaccine against Atherosclerosis

2021 ◽  
Vol 41 (06) ◽  
pp. 447-457
Author(s):  
Timoteo Marchini ◽  
Tijani Abogunloko ◽  
Dennis Wolf
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Experimental Atherosclerosis ◽  
Chronic Inflammatory Disease ◽  
Autoimmune Response ◽  
Atherosclerotic Plaques ◽  
Low Grade ◽  
Main Protein ◽  
Specific Antigens ◽  
Traditional Risk Factors

AbstractAtherosclerosis is a chronic inflammatory disease of the arterial wall that leads to the build-up of occluding atherosclerotic plaques. Its clinical sequelae, myocardial infarction and stroke, represent the most frequent causes of death worldwide. Atherosclerosis is a multifactorial pathology that involves traditional risk factors and chronic low-grade inflammation in the atherosclerotic plaque and systemically. This process is accompanied by a strong autoimmune response that involves autoreactive T cells in lymph nodes and atherosclerotic plaques, as well as autoantibodies that recognize low-density lipoprotein (LDL) and its main protein component apolipoprotein B (ApoB). In the past 60 years, numerous preclinical observations have suggested that immunomodulatory vaccination with LDL, ApoB, or its peptides has the potential to specifically dampen autoimmunity, enhance tolerance to atherosclerosis-specific antigens, and protect from experimental atherosclerosis in mouse models. Here, we summarize and discuss mechanisms, challenges, and therapeutic opportunities of immunomodulatory vaccination and other strategies to enhance protective immunity in atherosclerosis.

Glycation and HMG-CoA Reductase Inhibitors: Implication in Diabetes and Associated Complications

2019 ◽  
Vol 15 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Rabia Nabi ◽  
Sahir Sultan Alvi ◽  
Mohd. Saeed ◽  
Saheem Ahmad ◽  
Mohammad Salman Khan
Keyword(s):  
Oxidized Ldl ◽  
Advanced Glycation Endproducts ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Therapeutic Effects ◽  
Hmg Coa Reductase ◽  
Toxicological Effects ◽  
Coa Reductase

Introduction: Diabetes Mellitus (DM) acts as an absolute mediator of cardiovascular risk, prompting the prolonged occurrence, size and intricacy of atherosclerotic plaques via enhanced Advanced Glycation Endproducts (AGEs) formation. Moreover, hyperglycemia is associated with enhanced glyco-oxidized and oxidized Low-Density Lipoprotein (LDL) possessing greater atherogenicity and decreased the ability to regulate HMG-CoA reductase (HMG-R). Although aminoguanidine (AG) prevents the AGE-induced protein cross-linking due to its anti-glycation potential, it exerts several unusual pharmaco-toxicological effects thus restraining its desirable therapeutic effects. HMG-R inhibitors/statins exhibit a variety of beneficial impacts in addition to the cholesterol-lowering effects. Objective: Inhibition of AGEs interaction with receptor for AGEs (RAGE) and glyco-oxidized-LDL by HMG-R inhibitors could decrease LDL uptake by LDL-receptor (LDL-R), regulate cholesterol synthesis via HMG-R, decrease oxidative and inflammatory stress to improve the diabetes-associated complications. Conclusion: Current article appraises the pathological AGE-RAGE concerns in diabetes and its associated complications, mainly focusing on the phenomenon of both circulatory AGEs and those accumulating in tissues in diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy, discussing the potential protective role of HMG-R inhibitors against diabetic complications.

scholarly journals Pharmacokinetics, Distribution in Serum Lipoproteins and Tissues, and Renal Toxicities of Amphotericin B and Amphotericin B Lipid Complex in a Hypercholesterolemic Rabbit Model: Single-Dose Studies

1998 ◽  
Vol 42 (12) ◽  
pp. 3146-3152 ◽  
Author(s):  
Kishor M. Wasan ◽  
Allison L. Kennedy ◽  
Shawn M. Cassidy ◽  
Manisha Ramaswamy ◽  
Lorilynne Holtorf ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Ldl Cholesterol ◽  
Renal Toxicity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Total Serum ◽  
Lipid Complex ◽  
Blood Samples ◽  
Regular Diet ◽  
Cholesterol Levels

ABSTRACT The purpose of this study was to determine if a relationship exists among total serum and lipoprotein cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the serum pharmacokinetics of AmpB in hypercholesterolemic rabbits administered AmpB and AmpB lipid complex (ABLC). After 10 days of cholesterol-enriched diet (0.50% [wt/vol]) or regular rabbit diet (control), each rabbit was administered a single intravenous bolus of AmpB or ABLC (1.0 mg/kg of body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, kidney toxicity, and serum lipoprotein distribution. Rabbits were humanely sacrificed after all blood samples were obtained, and tissues were harvested for drug analysis. Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with levels in rabbits on a regular diet. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered AmpB. However, the magnitude of this increase was 2.5-fold greater in cholesterol-fed rabbits than in regular diet-fed rabbits. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered ABLC. Whereas AmpB pharmacokinetics were significantly altered in cholesterol-fed rabbits administered free AmpB, similar AmpB pharmacokinetics were observed in both rabbit groups administered ABLC. Renal AmpB levels were significantly increased in cholesterol-fed rabbits administered AmpB compared with those in all other groups. Hepatic and lung AmpB levels were elevated in cholesterol-fed rabbits administered free AmpB compared to controls. In addition, hepatic, lung, and spleen AmpB levels were significantly decreased in cholesterol-fed rabbits administered ABLC compared to controls. An increased percentage of AmpB was recovered in LDL–very-low-density lipoprotein fraction when free AmpB was administered to cholesterol-fed rabbits compared with those in all other groups. These findings suggest that increases in cholesterol, specifically, LDL cholesterol levels, modify the disposition and renal toxicity of free AmpB. However, the pharmacokinetics and renal toxicity of ABLC were independent of elevations in total and LDL cholesterol levels.

scholarly journals Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes

2016 ◽  
Vol 116 (09) ◽  
pp. 565-577 ◽  
Author(s):  
Gemma Brufau ◽  
Marion J. J. Gijbels ◽  
Ine M. J. Wolfs ◽  
Saskia van der Velden ◽  
Chantal C. H. Pöttgens ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Liver Cholesterol ◽  
Specific Cell ◽  
Low Density ◽  
Atherosclerosis Development ◽  
Deficient Mice

SummaryInflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Protective role of eclipta alba against hyperlipidemia induced by high-fat diet in albino rats

2019 ◽  
Vol 10 (2) ◽  
pp. 1181-1184
Author(s):  
Satheesh Naik K ◽  
Gurushanthaiah M ◽  
Nagesh Raju G ◽  
Lokanadham S ◽  
Seshadri Reddy V
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Albino Rats ◽  
High Fat ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Eclipta Alba ◽  
Wistar Strain

Eclipta Alba has been used in traditional and folklore medicine to treat Hyperlipidemia and hepatic disorders. The present study was aimed to investigate the Antihyperlipidemic and hepatoprotective potentials of Eclipta Alba in high-fat diet -induced Albino rats and to determine the underlying mechanism.  A total of 30 adult albino rats of Wistar strain weighing 165–215 g were utilized. Animals were treated with high-fat diet for 8 weeks followed by post-treatment of E. Alba for 1 week, 2 weeks, and 3 weeks, respectively. After 12 h of fasting on the last day of the experiment, serum blood samples were collected in EDTA vials and processed for biochemical analysis.  A significant decrease in levels of total cholesterol and triglycerides was noted on animals treated with E. alba compared to high-fat diet animals. Treatment of hypercholesterolemic rats with E. Alba showed a marked decrease of serum low-density lipoprotein (LDL) and very LDL cholesterol concentrations compared to the hypercholesterolemic rats. High-fat diet feeding worsened the levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase enzymes, whereas the same markers were significantly improved by supplementation with E. alba compared to the normal group.  E. alba acts as an antihyperlipidemic agent in hyperlipidemic conditions and helps for better health.

scholarly journals Anti-Obesity Effect of Galacto-Oligosaccharides in Obese Rats

2021 ◽  
Author(s):  
Shang Kong ◽  
Xingjun Huang ◽  
Hua Cao ◽  
Yan Bai ◽  
Qishi Che ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fat Body ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Protective Role ◽  
Lipoprotein Cholesterol ◽  
Fat Cells ◽  
Expression Levels ◽  
Brown Adipose ◽  
Obese Rats

Abstract Background: Galacto-oligosaccharides (GOS) is a commonly used as a prebiotic with a variety of metabolic benefits. Whether GOS plays a protective role in obesity is still unknown. Here we demonstrated that GOS possesses an anti-obesity activity by promoting adipose tissue browning and thermogenesis. Results: Our results showed that GOS effectively slow weight gain of diet-induced obese (DIO) rats without affecting energy intake. GOS significantly suppressed the hypertrophy and hyperplasia of white adipose tissue (WAT), as well as markedly lessened the ratio of fat pad to fat body. Consistently, GOS significantly improved serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels, which indicated an appropriate weight loss activity of GOS. Interestingly, GOS also significantly increased the expression levels of browning proteins (UCP1, PPARγ, PGC1α and PRMD16) both in the WAT and brown adipose tissue (BAT). We further found that GOS markedly increased the expression levels of LXRα, PPARα, LDLR and CYP7A1 proteins in the liver of obese rats. Conclusions: Taken together, we concluded that GOS inhibits obesity by accelerating the browning of white fat cells and the thermogenesis of brown fat cells, moreover GOS improves host lipid homeostasis by promoting cholesterol catabolism.

scholarly journals Macrophage NCOR1 protects from atherosclerosis by repressing a pro-atherogenic PPARγ signature

2019 ◽  
Author(s):  
Sara Oppi ◽  
Stefanie Nusser-Stein ◽  
Przemyslaw Blyszczuk ◽  
Xu Wang ◽  
Anne Jomard ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Myeloid Cell ◽  
Foam Cell Formation ◽  
Low Density ◽  
Enhanced Expression ◽  
Atherosclerosis Development

Abstract Aims Nuclear receptors and their cofactors regulate key pathophysiological processes in atherosclerosis development. The transcriptional activity of these nuclear receptors is controlled by the nuclear receptor corepressors (NCOR), scaffolding proteins that form the basis of large corepressor complexes. Studies with primary macrophages demonstrated that the deletion of Ncor1 increases the expression of atherosclerotic molecules. However, the role of nuclear receptor corepressors in atherogenesis is unknown. Methods and results We generated myeloid cell-specific Ncor1 knockout mice and crossbred them with low-density lipoprotein receptor (Ldlr) knockouts to study the role of macrophage NCOR1 in atherosclerosis. We demonstrate that myeloid cell-specific deletion of nuclear receptor corepressor 1 (NCOR1) aggravates atherosclerosis development in mice. Macrophage Ncor1-deficiency leads to increased foam cell formation, enhanced expression of pro-inflammatory cytokines, and atherosclerotic lesions characterized by larger necrotic cores and thinner fibrous caps. The immunometabolic effects of NCOR1 are mediated via suppression of peroxisome proliferator-activated receptor gamma (PPARγ) target genes in mouse and human macrophages, which lead to an enhanced expression of the CD36 scavenger receptor and subsequent increase in oxidized low-density lipoprotein uptake in the absence of NCOR1. Interestingly, in human atherosclerotic plaques, the expression of NCOR1 is reduced whereas the PPARγ signature is increased, and this signature is more pronounced in ruptured compared with non-ruptured carotid plaques. Conclusions Our findings show that macrophage NCOR1 blocks the pro-atherogenic functions of PPARγ in atherosclerosis and suggest that stabilizing the NCOR1–PPARγ binding could be a promising strategy to block the pro-atherogenic functions of plaque macrophages and lesion progression in atherosclerotic patients.

Sign in / Sign up

Export Citation Format

Share Document