Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that hyperbaric oxygen (HBO) treatment inhibits diet-induced atherosclerosis in New Zealand White rabbits. In the present study we investigate the mechanisms that might be involved in the athero-protective effect of HBO treatment in a well-accepted model of atherosclerosis, the apoE knockout (KO) mouse. We examine the effects of daily HBO treatment (for 5 and 10 weeks) on the components of the anti-oxidant defense mechanism and the redox state in blood, liver and aortic tissues and compare them to those of untreated apoE KO mice. HBO treatment results in a significant reduction of aortic cholesterol content and decreased fatty streak formation. These changes are accompanied by a significant reduction of autoantibodies against oxidatively modified LDL and profound changes in the redox state of the liver and aortic tissues. A 10-week treatment significantly reduces hepatic levels of TBARS and oxidized glutathione, while significantly increases the levels of reduced glutathione, glutathione reductase (GR), transferase, Se-dependent glutathione peroxidase and catalase (CAT). The effects of HBO treatment are similar in the aortic tissues. These observations provide evidence that HBO treatment has a powerful effect on the redox state of relevant tissues and produces an environment that inhibits oxidation. The anti-oxidant response may be the key to the anti-atherogenic effect of HBO treatment.
Atherosclerosis 2007 Jul
PMID:Chronic hyperbaric oxygen treatment elicits an anti-oxidant response and attenuates atherosclerosis in apoE knockout mice. 1697 70

This review focuses on the morphological features of atherosclerosis and the involvement of oxidative stress in the initiation and progression of this disease. There is now consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein in the vascular wall. Reactive oxygen species (ROS) are key mediators of signaling pathways that underlie vascular inflammation in atherogenesis, starting from the initiation of fatty streak development, through lesion progression, to ultimate plaque rupture. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction and stroke. Many data support the notion that ROS released from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase (MPO), xanthine oxidase (XO), lipoxygenase (LO), nitric oxide synthase (NOS) and enhanced ROS production from dysfunctional mitochondrial respiratory chain, indeed, have a causatory role in atherosclerosis and other vascular diseases. Moreover, oxidative modifications in the arterial wall can contribute to the arteriosclerosis when the balance between oxidants and antioxidants shifts in favour of the former. Therefore, it is important to consider sources of oxidants in the context of available antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase and transferases thiol-disulfide oxidoreductases and peroxiredoxins. Here, we review also the mechanisms in which they are involved in order to accelerate the pace of the discovery and facilitate development of novel therapeutic approaches.
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PMID:Atherosclerosis and oxidative stress. 1807 94

Retroviral gene transfer and bone marrow transplantation has been used by many investigators to study the role of macrophage proteins in different mouse models of human disease. While this approach is faster and less expensive than generating transgenic mice with macrophage-specific promoters and applicable to a wider array of mouse models, it has been hampered by two major drawbacks: labor-intensive cloning procedures involved in generating retroviral vectors for each gene of interest and low viral titers. Here we describe the construction of a MSCV-based retroviral vector that can serve as an acceptor vector for commercially available Cre-lox-compatible donor vectors. Using this new retroviral vector in combination with a FACS approach to enhance viral titers, we generated high-titer retroviruses carrying either EGFP-tagged cytosolic or EGFP-tagged mitochondria-targeted glutathione reductase. We show that the introduction of these constructs via retroviral gene transfer and bone marrow transplantation into atherosclerosis-prone LDL receptor-null mice results in the long-term increase in macrophage glutathione reductase activity.
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PMID:Generation of retroviruses for the overexpression of cytosolic and mitochondrial glutathione reductase in macrophages in vivo. 1900 13

The primary cause of morbidity and mortality in renal transplantation is cardiovascular disease. Increased oxidative stress implies a greater degree of atherogenesis in these patients. N-acetylcysteine (NAC) which has a thiol group that is the source of l-cysteine and reduced glutathione, acts against atherosclerosis via a decrease in apoptosis, vasoconstriction, and endothelial dysfunction. Experimental models have examined the antioxidant effects of NAC during and after ischemia-reperfusion, but few studies have shown an effect in renal transplantation in human beings. In 8 months, we studied the effect of NAC treatment on oxidative stress, lipids, and renal function in 25 patients with stable renal function and no diabetes after transplantation. Data were collected on oxidative parameters: malondialdehyde, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, lipid profile, and renal function (creatinine concentration, Cockroft-Gault formula, and Modified Diet in Renal Disease study). There were no significant differences in oxidative profile before and after treatment with NAC. The mean serum high-density lipoprotein cholesterol fraction increased after treatment and showed a significant positive correlation with glutathione peroxidase (r = 0.495). Serum creatinine concentration decreased, and Cockroft-Gault and Modified Diet in Renal Disease study estimates of renal function increased in the treatment period. In conclusion, NAC treatment in patients with stable renal function after transplantation increased high-density lipoprotein cholesterol and antioxidant molecules in relation to glutathione peroxidase, with a positive influence on renal function.
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PMID:Treatment with N-acetylcysteine in stable renal transplantation. 1901 Jan 40

Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis. It is hypothesized that these medications may improve blood pressure and serum cholesterol by modifying the antioxidative status and energy metabolism of erythrocytes. In this study, the effects of 2 treatments are compared: lisinopril alone versus lisinopril + simvastatin, on erythrocyte antioxidant and energy metabolic enzymes. Patients with atherosclerosis and moderate hypertension are randomly assigned to receive lisinopril 10 to 20 mg/d or lisinopril 10 to 20 mg/d plus simvastatin 20 mg/d for 24 weeks. Higher catalase activity and lower glutathione peroxidase activity are observed in 94% to 100% patients from both groups after 12 and 24 weeks of treatment. Superoxide dismutase activity is increased significantly only after 24 weeks. No changes of glutathione reductase, lactate dehydrogenase, and phosphofructokinase activities are found under any conditions indicated. Both treatments decrease systolic and diastolic blood pressure equally. Only lisinopril + simvastatin treatment decreases plasma total cholesterol and low-density lipoprotein cholesterol. The results show for the first time that lisinopril monotherapy and combined lisinopril + simvastatin therapy exhibit specific and pronounced effects on antioxidant and energy metabolic enzyme activities in erythrocytes of hypertensive patients.
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PMID:Specific and pronounced impacts of lisinopril and lisinopril plus simvastatin on erythrocyte antioxidant enzymes. 1984 Nov 60

Protective effects of blueberries (BB) against atherosclerosis and potential underlying mechanisms in reducing oxidative stress were examined in apoE-deficient (apoE(-/-)) mice. ApoE(-/-) mice were fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried whole BB for 20 wk. The mean lesion area for apoE(-/-) mice fed BB was reduced by 39% (P < 0.001) in the aorta sinus and 58% (P < 0.001) in the descending aorta compared with CD-fed mice. These atheroprotective effects were independent of the serum lipid profile or total antioxidant capacity (as measured by oxygen radical absorbance capacity). The concentration of a biomarker of lipid peroxidation, F(2)-isoprostane, was lower in liver of BB-fed mice (P < 0.05). Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. Enzyme activities of SOD and GSR were greater (P < 0.05) in liver and/or serum of BB-fed mice than those of CD-fed mice. In addition, serum paraoxonase 1 activity in serum of BB-fed mice was also greater than that of CD-fed mice (P < 0.05) at the end of the study. These results suggest a protective effectiveness of BB against atherosclerosis in this apoE(-/-) mouse model. The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.
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PMID:Dietary blueberries attenuate atherosclerosis in apolipoprotein E-deficient mice by upregulating antioxidant enzyme expression. 2066 Feb 83

Rice-based diets may have been reported to protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of rice-based diet was addressed using the apolipoprotein E knockout (apoE-/-) mice fed rice protein isolate (RPI) or casein (CAS). Reduced atherosclerotic lesions were observed in aortic sinus and enface analyses of the descending aorta in RPI-fed apoE-/- mice compared with CAS-fed mice. Plasma total- and HDL-cholesterol levels were not different amongst the two groups, suggesting alternative mechanism(s) could have contributed to the atheroprotective effect of rice-based diets. Plasma oxLDL and anti-oxLDL IgG levels were significantly decreased in RPI-fed compared to CAS-fed animals. Plasma and aortic tissue GSH levels and GSH:GSSG ratio were higher in RPI-fed mice compared to CAS-fed group. Interestingly, RPI feeding increased mRNA and protein expression of superoxide dismutase, and mRNA expression of catalase, glutathione peroxidase and glutathione reductase, key antioxidant enzymes implicated inhibiting oxidative stress leading to atherosclerosis. In conclusion, these findings suggest that the reduction in atherosclerotic lesions observed in mice fed the rice-based diet is mediated in part by inhibiting oxidative stress and subsequent oxLDL generation that could result in reduced foam cell formation, an early event during atherogenesis.
Atherosclerosis 2010 Sep
PMID:Dietary rice protein isolate attenuates atherosclerosis in apoE-deficient mice by upregulating antioxidant enzymes. 2083 91

Oral ingestion of monosodium glutamate (MSG) to chronic alcoholic adult male mice at dose levels of 4 and 8 mg/g body weight for seven consecutive days caused a significant increase in lipid fractions, lipid peroxidation, xanthine oxidase, whereas the levels of superoxide dismutase, catalase, glutathione, and its metabolizing enzymes like glutathione peroxidase and glutathione reductase were significantly decreased in the arterial tissue. These observations suggested that ingestion of MSG to chronic alcoholic animals had no beneficial effect and thereby, could act as an additional factor for the initiation of atherosclerosis.
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PMID:Effect of monosodium glutamate on various lipid fractions and certain antioxidant enzymes in arterial tissue of chronic alcoholic adult male mice. 2273 96

Smoking cigarettes and alcohol addiction are serious problems in health hazard and life of society. Tobacco smoke leads to many kinds of cancer formation and scientific research indicates, that heart-vascular disease and lung cancer are the most common diseases caused by tobacco smoke. While talking about ethanol, it is responsible for liver, pancreas, mucous membrane damage and leads to central and circular nervous disorder. Scientific research indicates, that many smokers drink alcohol and vice versa. Unfortunately in that case the risk of many diseases increases. Both of these stimulants leads to enlarged production of reactive oxygen species, which is connected with unbalance between pro and antioxidant processes in human organism. Free radicals in normal conditions plays positive role but with tobacco smoke and alcohol connection may lead to serious changes in human organism. They damage organs, it comes to protein structure, nucleic acid and fat violation, which in consequence leads to immunity decrease and many pathological changes. Reactive oxygen species also plays role in pathogenesis of many diseases: diabetes mellitus, atherosclerosis and Down syndrome. ROS may also increase the risk of pancreas, lung, larynx and urinary bladder cancer formation. Human organism defends oneself from harmful influence of reactive oxygen species owing to enzymatic and non-enzymatic systems presence-Non-enzymatic antioxidants: glutathione, carotene, bilirubin, tocopherol, uric acid and ions metals temporary complex belong to non-enzymatic systems. To enzymatic ones belong: catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase. The aim of the study was tobacco smoke and ethyl alcohol influence evaluation in rats addicted to these substances on activity of chosen enzymes responsible for organism defense against toxic compounds action. To this study 63 white, Wistar tribe rats at the age of 3,5 months were used - males addicted to ethyl alcohol. They were divided into 3 groups, each consist of 21 rats. Animals of Group I were exposed on harmful tobacco smoke influence. Group II constitute animals, which were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. The next Group - III, in which animals at first were exposed on tobacco smoke influence. When exposition was over, animals were given by stomach probe 10% alcohol dilution once at a dose of 2 g/kg weight. Depending on the type of marker and studied organ, changes in the levels of selected enzymes, responsible for defending organism against reactive forms of oxygen has been shown. Both tobacco smoke and ethyl alcohol resulted in a change of glutathione levels in the serum and tissues of animals. Tobacco smoke has the biggest influence on protein nitrozylation in the brain and ethyl alcohol had influence on glutathione level in serum, kidney, brain and superoxide dismutase activity in the brain. Application of many oxidative stress markers allows for evaluation of its differential influence on various organs.
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PMID:[Selected biochemical parameters of oxidative stress as a result of exposure to tobacco smoke in animals addicted to ethyl alcohol]. 2342 Oct 41

Even though the role of all-trans lycopene from tomato in controlling atherosclerosis was reported, but no report is available on the cis-isomer of lycopene obtained from an easily available source green algae Chlorella marina. So in this study, Sprague Dawley rats fed with high-cholesterol diet were given standard drug lovastatin; algal lycopene (AL) (cis/all-trans 40:60) and tomato all-trans lycopene (TL) and the following parameters were studied. Total cholesterol, low-density lipoprotein, triglycerides were decreased significantly and the high-density lipoprotein levels were increased on treatment with AL. The activities of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase were found to be increased, whereas thiobarbituric acid reactive substances levels were decreased in AL when compared to the drug and TL-treated rats. The activities of inflammatory marker enzymes like cyclooxygenase, 15-lipoxygenase in monocytes and myeloperoxidase, C-reactive protein and ceruloplasmin levels in serum were found to be decreased on treatment with AL. Histopathological studies revealed that lycopene from this alga could reduce fatty liver and aortic plaque when compared to the drug and TL. Algal lycopene showed very significant antioxidant and anti-inflammatory effect in high-cholesterol fed rats. Therefore, AL from C. marina would be recommended for the treatment of hyperlipidemia.
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PMID:Effect of lycopene from Chlorella marina on high cholesterol-induced oxidative damage and inflammation in rats. 2388 96


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