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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a new assay for antioxidant activity (AOA) in lipoprotein solutions based upon their potential to quench light emission from a glowing horseradish peroxidase-catalyzed enhanced chemiluminescent reaction. By comparison with the quenching activity of the tocopherol-analogue trolox the AOA can be quantified. These measurements suggest that all lipoprotein fractions have significant AOA and that this has a non-linear relationship with lipoprotein concentration increasing significantly on a per particle basis at higher concentrations. Mean AOA in very low density, low density and high density lipoprotein fractions were 39.9 +/- 5.3, 20.3 +/- 4.0 and 5.3 +/- 1.0 mumol of trolox equivalents per litre, respectively, when measured at 1 mg protein/ml. Using known values for the protein content of the lipoprotein fractions, these values correspond to 79.8 +/- 10.7, 10.3 +/- 2.0 and 0.84 +/- 0.15 equivalents per particle. Parallel measurements of light emission and conjugated diene formation suggest that the oxidative stress imposed by the peroxidase-catalyzed reaction leads to lipid peroxidation but only after all AOA has been exhausted. AOA was significantly correlated with the alpha-tocopherol content in 30 lipoprotein samples (r = 0.764). This assay offers a rapid and simple method for investigating the effects of diseases, drugs or dietary manipulation on lipoprotein AOA.
Atherosclerosis 1994 Nov
PMID:Measurement of antioxidant activity in lipoproteins using enhanced chemiluminescence. 784 Aug 16

Oxygen free radicals (OFR) are very reactive and unstable metabolites capable of altering important biomolecules including proteins, lipids and nucleic acids. OFR are regulated by enzymes such as superoxide dismutases (SOD), catalase, glutation peroxidase and by molecules such as vitamins E, A, C, and K, selenio, cystein and other compounds. Increased OFR levels due to an overproduction of these metabolites or to a failure in the control system, induce cellular and tissue injuries that could lead to diseases such as atherosclerosis, arthritis, fibrosis, lung and heart injuries, neurological disorders and cancer. In this article we consider the use of SOD as therapeutic agents both in human and experimental models. We also refer to the administration of SOD as a protective factor against secondary injuries during radiotherapy and to the determination of SOD as a tumor marker.
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PMID:[Free radicals of oxygen and superoxide dismutase. Biological and medical aspects]. 799 Jun 89

Oxidation of human plasma lipoprotein (LP) was studied in the presence of exogenous hypochlorite anion (OCl-) or OCl- generated in the "myeloperoxidase + H2O2 + Cl-" system. OCl- effectively initiates peroxidation of lipids extracted from LP and those within LP particles, as can be judged from accumulation of secondary (thiobarbituric acid [TBA] reactive) and final (Schiff bases) products of lipid peroxidation (LPO) in LP after incubation with myeloperoxidase or exogenous OCl-. Very low density and low density lipoproteins classified as atherogenic LP are more sensitive to OCl(-)-induced LPO than high density lipoproteins. These data allow us to propose that OCl- secreted by activated neutrophils and monocyte-macrophages can produce oxidative modification of LP in vivo. The latter is known as a risk factor in the development of atherosclerosis.
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PMID:Peroxidation of human blood lipoproteins induced by exogenous hypochlorite or hypochlorite generated in the system of "myeloperoxidase + H2O2 + Cl-". 800 9

The determination of lipid hydroperoxides in plasma and lipoproteins recently reached a clinical relevance in disorders such as atherosclerosis, where oxidative reactions have been suggested to play a fundamental pathogenetic role. The peroxide content of lipoproteins is usually measured after ultracentrifugation and extraction. During this procedure, some peroxides might decompose causing a too low recovery. To screen this possibility, the disappearance, in the presence of human plasma, of hydroperoxides of linoleic acid and Cu-oxidized low density lipoprotein (LDL) have been investigated, using both a iodometric titration and an enzymatic assay. While only in the presence of GSH plasma decomposes linoleic acid hydroperoxides quite rapidly, peroxides in Cu-oxidized LDL were stable both in presence as well as in absence of GSH. This indicated that lipid hydroperoxides are stable in plasma and that peroxides of Cu-oxidized LDL are not substrate for the glutathione-dependent peroxidase activity in plasma. The relevant decrease of the iodometric titre of LDL peroxides observed in the presence of elevated amounts of plasma was shown to be artifactual, since some compounds extracted from plasma do react with iodine generated by peroxides. Whole plasma itself, indeed, has been shown to reduce back to I- appreciable amount of free iodine.
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PMID:Effect of plasma on the degradation of hydroperoxides of unesterified linoleic acid and copper-peroxidized LDL. 800 31

Inflammatory reactions induce the production of reactive oxygen species (ROS): the reverse sequence of these events is also true. Moreover, many components of these reactions interact with a synergistic effect. In this short comprehensive review we analyze some of these interactions which may have pathological effects. Inflammatory reactions are triggered off by exogenous or endogenous aggressions and are characterized by cellular and vascular events. The activated leucocytes leave the circulating blood and reach the site of the aggression where they release a large amount of ROS as well as the content of their granules. The granular content is made in a large part by molecules with killing and degradative activities such as myeloperoxidase, defensins, elastase, collagenase, cathepsins and lysozyme. The inflammatory reaction is beneficial for humans when its effects are limited to the pathogens. The insufficiency of a component of the inflammatory reaction such as the production of ROS which is seen, for example in chronic granulomatous disease, leads to severe and recurrent bacterial infections. In other situations inflammatory reactions are deleterious because they are directed against normal tissues instead or in addition to pathogens. In some cases the behaviour of the phagocytes is modified because they have been primed by inflammatory molecules such tumor necrosis factor, LPS, interleukins or interferons. Priming often leads to a decreased speed of locomotion of the leucocytes with an increased susceptibility to their stimuli. The combination of these effects leads to a premature release by the phagocytes of their killing and degradative factors. Production of ROS such as that seen during irradiation, drug metabolism, or ischemia followed by reperfusion for example, induces inflammatory reactions with a secondary amplification of ROS production. Acute ROS production can also lead to thrombosis, whereas chronic ROS production can induce a chronic inflammatory reaction of the endothelium with atherosclerosis as a possible consequence. Some examples are also given to show that ROS might control positively or negatively the activity of inflammatory molecules. The multiplicity of the cross reactions between ROS and inflammation allows to suggest that drugs that disconnect these two events might be therapeutically used.
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PMID:[Reactive oxygen species and inflammation]. 801 8

Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall.
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PMID:Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. 804 Feb 85

Several recent postmortem studies suggest an increased prevalence of atherosclerosis in young habitual cocaine abusers. However, little is known about the effects of cocaine abuse on the vascular endothelium and its relationship to atherosclerosis. Therefore, the consequence of chronic administration of intravenous cocaine on the induction of aortic sudanophilia was examined. Male New Zealand White rabbits were fed a 0.5% cholesterol diet for 10 wk. During this period, animals were randomized to receive either cocaine-hydrochloride (0.25 mg/kg) intravenously (n = 17) twice daily; or an equivalent volume of 0.9% physiologic saline, control group (n = 16). Mean values for total circulating leukocytes and platelets and total plasma cholesterol and triglycerides were similar in both groups throughout the protocol. At the completion of the study, aortic sudanophilia was measured and expressed as a percentage of regional involvement (R1 = proximal 4 cm, R2 = middle 6 cm, and R3 = distal 10 cm). Statistical significance among groups was achieved in the proximal thoracic aorta (p = 0.057). No significant differences in sudanophilia were noted in the middle and distal segments. When animals were placed in subgroups according to percent total plaque involvement, there was a significant increased distribution of rabbits with a greater extent of sudanophilia in the cocaine-treated group as compared with control (p = 0.01, chi-square analysis). Immunocytochemical studies using the macrophage-specific and muscle actin-specific monoclonal antibodies demonstrated that sudanophilic areas in both groups were predominantly composed of macrophage-derived foam cells. Evaluation of plaque morphology showed an increase in intimal plaque thickness and in the number of macrophages and smooth muscle cells in cocaine-treated animals; however, group differences were not statistically significant. Because no significant differences were found in the cellular composition of atherosclerotic plaques between groups, further studies were performed to assess the effects of cocaine on the permeability function of cultured endothelial cell monolayers as a possible mechanism of increased sudanophilia. Cocaine (100 microM)-treated endothelial cell monolayers demonstrated an increased permeability to horseradish peroxidase during all time intervals studied (0-6 hr). Permeability differences were statistically significant at 30 min and 1 hr (p = 0.003 and 0.02, respectively). Collectively, these observations suggest that administration of cocaine to cholesterol-fed rabbits increases the prevalence of aortic sudanophilia via at least one possible mechanism involving enhanced vascular permeability.
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PMID:Increased prevalence of aortic fatty streaks in cholesterol-fed rabbits administered intravenous cocaine: the role of vascular endothelium. 811 19

Lipid metabolism and lipid peroxidation (LPO) were studied in residents of St. Petersburg (healthy subjects without atherosclerosis history, healthy relatives of atherosclerotic patients, postmyocardial infarction patients, post-apoplectic patients and coronary heart disease sufferers) versus matched subjects living in rural area. Altogether 215 patients were examined. Besides genotype factors, lipid metabolism and LPO were found responsive to environmental factors. These were especially potent in changing the activity of superoxide dismutase, glutathione peroxidase, catalase. In those living in the country myeloperoxidase, superoxide dismutase and catalase activity was higher than in city population. The latter exhibited, though, higher activity of glutathione peroxidase. It is evident that more advantageous ecological conditions have distinct antiatherogenic action on lipid metabolism and LPO, especially, suggesting possible treatment of atherosclerosis by moving to more healthy locality as regards environmental pollution.
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PMID:[The effect of heredity and environmental conditions on the development of atherogenic metabolic shifts]. 829 33

Population kinetics of monocytes (MC) was studied to prove their participation in atherogenesis. Increased number of cells containing lipids (CCL) in patients with severe stable angina pectoris is demonstrated (42.5 versus 7.4% in healthy persons). This is followed by MC esterase activity enhancement. In patients with angina of effort new types of MC appear (with high peroxidase and low esterase activity) and there is a drastic increase of CCL (more than 56%). The correlation between the number of CCL and indices of blood lipid metabolism in anginal patients is lacking. The results obtained may serve as a criterion for evaluating the degree and exacerbation of coronary atherosclerosis in humans.
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PMID:[Population kinetics of circulating monocytes in health and in patients with ischemic heart disease]. 831 11

Several findings pint out the occurrence of a strict relationship between lipoproteins and immunoresponsiveness. In this regard, in vitro lipoproteins pretreatment of mononuclear cell suspensions leads to an inhibition of Natural Killer (NK) cytotoxicity or T- and B-mediated immune functions. These results have an in vivo counterpart, since an impairment of either T-driven B cell polyclonal differentiation or phagocyte chemotaxis, phagocytosis and killing has been shown in patients with type IIa and type IIb primary hyperlipoproteinaemia. On the contrary, these activities fall within normal range in type IV hyperlipoproteinaemic subjects. To further address the potential role of polymorphonuclear cells (PMN) in atherosclerotic process, in the present report PMN-mediated superoxide anion (O2-) generation, hydrogen peroxide (H2O2) production, beta-glucuronidase and myeloperoxidase release have been assessed in similar groups of patients. Results provide a clearcut evidence for a significant enhancement of oxidative metabolism by either suspended or adherent to plastic PMN in type IIa primary hyperlipoproteinaemia only. These data were further confirmed by the observation that the same cell suspensions exhibit a significant increase of H2O2 generation and/or beta-glucuronidase and myeloperoxidase release. By contrast, PMN metabolic pathway in type IIb and type IV patients mimics that observed in healthy individuals. In the light of the well known increase of serum low-density lipoproteins (LDL) in type IIa primary hyperlipoproteinaemia, these findings suggest that also PMN may play an important role in the development of atherosclerosis. The augmented oxidative responsiveness may, in fact, give rise to LDL oxidation, which is in turn responsible for foam cell generation through an exaggerated uptake of oxidized LDL by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidative burst and lysosomal enzyme release by polymorphonuclear cells in type IIa, type IIb and type IV primary hyperlipoproteinaemia. 835 3


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