UMLS:C0004153 - FACTA Search

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

Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P</=0.001) in the treated group, suggesting the activation of reducing mechanisms.
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PMID:Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia. 1117 Dec 88

The most important risk factors contributing to the development of atherosclerosis include lipid disorders and the predisposition to early ischaemic heart disease in the family. Atherosclerotic process proceeds with age and it develops as a result of oxide LDL modification at the level of vascular wall. Oxygen-free radicals take part in this process, which may probably be opposed by the antioxidant system of the body. The aim of this study was to compare the intensity of lipid peroxidation and the activity of antioxidant enzymes in children from the families with the risk of early atherosclerosis and in children without such predisposition. The activity of katalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined and the concentration of malonic dialdehyde--a lipid peroxidation marker was established. The study was conducted on 76 children aged 4-17 years, mean age 12 +/- 0.6 years. The risk group consisted of 56 patients with the history of hypercholesterolaemia and early atherosclerosis in the members of their families up to 45 years of age. Control group was formed of 20 subjects without such history. MDA concentration as well as the activity of antioxidant enzymes were determined with the use of adequate methods of spectrophotometry. The results obtained were subject to statistical analysis. The activity of antioxidant enzymes displayed considerable fluctuations in both groups of children, but these differences remained statistically insignificant in all the cases. Higher MDA concentrations in serum and in erythrocytes were observed in the risk group. These differences proved statistically significant (alpha < 0.05). On the basis of the present study and the analysis performed, it was found that the activity of antioxidant enzymes (CAT, SOD, GSH-Px) cannot serve as a parameter differentiating between children from the families with the risk of early atherosclerosis and children without such predisposition. Children with positive family history of hypercholesterolaemia and early atherosclerosis may demonstrate intensive lipid peroxidation, but this hypothesis requires further investigations.
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PMID:Enzymatic efficiency of erythrocyte antioxidant barrier and lipid peroxidation in children from families with high risk of early atherosclerosis. 1120 96

Reactive oxygen species (ROS) are implicated in the pathophysiology of a number of vascular disorders, including atherosclerosis. Recent studies indicate that ROS modulate signal transduction in mammalian cells. Previously, we have shown that ROS (hydrogen peroxide, fatty acid hydroperoxide, diperoxovanadate, and 4-hydroxynonenal) enhance protein tyrosine phosphorylation and activate phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAECs). In the present study, our aim was to investigate the role of exogenous thiol agents on ROS-induced PLD activation in conjunction with the role of cellular thiols--glutathione (GSH) and protein thiols--on PLD activation and protein tyrosine phosphorylation. Pretreatment of BPAECs with N-acetyl-L-cysteine (NAC) or 2-mercaptopropionylglycine (MPG) blocked ROS-induced changes in intracellular GSH and PLD activation. Also, pretreatment with NAC attenuated diperoxovanadate-induced protein tyrosine phosphorylation. Pretreatment of BPAECs with diamide or L-buthionine-(S,R)-sulfoximine (BSO), agents that lower intracellular GSH and thiols, enhanced PLD activity. Furthermore, NAC blocked diamide- or BSO-mediated changes in GSH levels, PLD activity, and protein tyrosine phosphorylation. NAC also attenuated diamide-induced tyrosine phosphorylation of proteins between 69 and 118 KDa. These results support the hypothesis that modulation of thiol-redox status (cellular nonprotein and protein thiols) may contribute to the regulation of ROS-induced protein tyrosine phosphorylation and PLD activation in vascular endothelium.
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PMID:Phospholipase D activation in endothelial cells is redox sensitive. 1122 47

Recent studies have proposed a role for a reduced number of circulating monocytes in the development of atherosclerosis and circulatory diseases in diabetes. Ketosis is frequently encountered in type-I diabetics. This study was undertaken to test the hypothesis that hyperketonemia can lower blood monocyte count in type-I diabetic patients. Blood monocyte count was significantly lower (p < 0.05) in diabetics (n = 27) compared with age-matched normal siblings (n = 22). Blood levels of acetoacetate (AA) and triglycerides were significantly higher in diabetics compared with normals. To examine whether hyperketonemia can directly alter the monocyte count in diabetics, we studied the effect of ketone bodies AA and beta-hydroxybutyrate (BHB) on U937 cells, a human-derived promonocytic cell line as an in vitro model. The cell culture studies showed a dose-dependent growth inhibition and induction of apoptosis as a result of treatment with AA in U937 cells. Furthermore, there was a significant decrease in GSH and increase in lipid peroxidation products in AA-treated U937 cells. Taken together, this study suggests that elevated levels of ketone body AA can result in oxidative damage, accelerated apoptosis, and inhibition of cell growth in monocytes, which in turn can lower monocyte count in the blood of type-I diabetic patients.
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PMID:Effect of hyperketonemia on blood monocytes in type-I diabetic patients and apoptosis in cultured U937 monocytes. 1122 48

Oxidative modification of LDL has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, we determined the effects of aged garlic extract (AGE) and its major compound, S-allylcysteine (SAC), on oxidized LDL (Ox-LDL)-induced injury in endothelial cells (EC). Lactate dehydrogenase (LDH) release as an index of membrane damage, methylthiazol tetrazoium (MTT) assay for cell viability and thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation were measured. Ox-LDL caused an increase of LDH release, loss of cell viability and TBARS formation. Both AGE and SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or SAC on intracellular glutathione (GSH) level in EC, and release of peroxide from EC and macrophages (M Phi) were determined. Ox-LDL depleted intracellular GSH and increased release of peroxides. Both AGE and SAC inhibited these changes. Effects of SAC on hydrogen peroxide (H(2)O(2)) or tumor necrosis factor (TNF)-alpha-induced nuclear factor (NF)-kappa B activation were determined. Pretreatment of EC with SAC inhibited NF-kappa B activation. We demonstrated that both AGE and SAC can protect EC from Ox-LDL-induced injury by preventing intracellular GSH depletion in EC and by minimizing release of peroxides from EC and M Phi. SAC also inhibited H(2)O(2)- or TNF-alpha-induced NF-kappa B activation. Our data suggest that AGE and its main compound, SAC, may be useful for prevention of atherosclerosis.
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PMID:Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation. 1123 9

Reduced glutathione (GSH) plays a critical role as an intracellular defense system providing detoxification of a broad spectrum of reactive species and their excretion as water-soluble conjugates. Conjugation of GSH with electrophiles is catalyzed by GSH S-transferases (GST), which constitute a broad family of phase II isoenzymes. Two of the GST encoding genes, GSTM1 (mu) and GSTT1 (theta), have a null genotype due to their homozygous deletion that results in lack of active protein. Polymorphisms within GSTT1 and especially GSTM1 have often been associated with cancer in various organs as well as with elevated levels of DNA adducts in various cell types. We recently demonstrated that DNA adducts are consistently detectable in smooth muscle cells (SMC) of human abdominal aorta affected by atherosclerotic lesions. Here we provide evidence that levels of adducts to SMC DNA from atherosclerotic lesions are consistently increased in individuals having the null GSTM1 genotype, whereas no association was established with the GSTT1 polymorphism. The influence of GSTM1 deletion was better expressed in never-smokers and ex-smokers than in current smokers. These findings bear relevance to the epidemiology of atherosclerosis and suggest that metabolic polymorphisms may contribute to the interindividual variability in susceptibility not only to carcinogens, but also to DNA binding atherogens.
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PMID:Increased DNA alterations in atherosclerotic lesions of individuals lacking the GSTM1 genotype. 1125 93

Although the accumulation of vascular endothelial growth factor (VEGF) has been observed in human atherosclerotic lesions, the exact role of this growth factor in atherogenesis remains unknown. We hypothesized that VEGF in the vascular wall might have a preventive effect on endothelial cell damage during atherosclerosis. To test our hypothesis, we examined whether VEGF protects against the toxicity of oxidized low density lipoprotein (Ox-LDL) in cultured endothelial cells derived from bovine aortas (BAECs). Preincubation of BAECs with VEGF prevented Ox-LDL-induced toxicity in a preincubation time- and VEGF concentration-dependent manner. Addition of N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, did not reverse the protective effect of VEGF on Ox-LDL toxicity. Incubation of BAECs with VEGF increased intracellular glutathione (GSH) content in a time-dependent manner. Combined addition of VEGF and L-buthionine sulfoximine, a GSH synthesis inhibitor, reversed both GSH levels and the protective effect of VEGF on Ox-LDL-induced cytotoxicity. Placenta growth factor, which ligates to the VEGF Flt-1 receptor but not KDR/Flk-1, failed to prevent Ox-LDL toxicity and had no effect on intracellular GSH levels. An anti-KDR antibody completely blocked these beneficial activities of VEGF. These results suggest that VEGF prevents Ox-LDL-induced endothelial cell damage via an intracellular GSH-dependent mechanism through the KDR/Flk-1 receptor.
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PMID:VEGF protects against oxidized LDL toxicity to endothelial cells by an intracellular glutathione-dependent mechanism through the KDR receptor. 1134 72

Endogenous oxygen- and nitrogen-centered free radicals are considered to play a decisive role in a variety of diseases such as neurodegenerative disorders, atherosclerosis, or cancer. Directly operating antioxidants limit the action of freely diffusing radicals by scavenging the attacking, oxidizing radical and re-reducing the oxidized biomolecule, i.e., the biomolecule-derived radical. From textbooks of biochemistry it is understood that NAD(P)H acts as a hydride (hydrogen anion) donor in a variety of enzymatic processes. One example is the re-reduction of GSSG to GSH, catalyzed by glutathione reductase. Because of this reaction, NADPH has been suggested to also act as an indirectly operating antioxidant, thus maintaining the antioxidative power of glutathione. To the best of our knowledge, however, neither NADPH nor NADH has been considered to be directly operating antioxidants. Based on recently published data, new experiments, and theoretical considerations, we propose that NAD(P)H represents a decisive, directly operating antioxidant that should be considered of major importance in the mitochondrial compartment. NAD(P)H fulfills this task both by scavenging toxic free radicals and repairing biomolecule-derived radicals.
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PMID:NAD(P)H, a directly operating antioxidant? 1142 89

This study has been initiated to investigate, in hypercholesterolaemic rabbits, whether L-carnitine deficiency could be an additional risk factor in atherosclerosis, and if so, whether L-carnitine supplementation could prevent the progression of atherosclerosis. Hypercholesterolaemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days, whereas, carnitine deficiency was induced by daily i.p. administration of 250 mg kg(-1) of D-carnitine for 28 days. Histopathological examination of aorta and coronaries from hypercholesterolaemic rabbits revealed severe atherosclerotic lesions, intimal plaques and foam cell formation. Also, hypercholesterolaemic diet resulted in a significant 53 and 43% decrease in reduced glutathion (GSH) levels and a significant (1.87-fold) and (14.1-fold) increase in malonedialdhyde (MDA) levels in aorta and cardiac tissues, respectively. Daily administration of L-carnitine (250 mg kg(-1)) for 28 days, completely prevented the progression of atherosclerotic lesions induced by hpercholesterolaemia in both aorta and coronaries. Conversely, daily administration of D-carnitine (250 mg kg(-1)) for 28 days increased the progression of atherosclerotic lesions with the appearance of foam cells and apparent intimal plaques which are even larger than that seen in hypercholesterolaemic rabbits. Both L-carnitine and D-carnitine produced similar effects on the lipid profile, GSH and MDA which may point to the conclusion that: (1) L-carnitine prevents the progression of atherosclerotic lesions by another mechanism in addition to its antioxidant and lipid-lowering effects; (2) endogenous carnitine depletion and/or carnitine deficiency should be viewed as an additional risk factor in atherogenesis.
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PMID:L-carnitine prevents the progression of atherosclerotic lesions in hypercholesterolaemic rabbits. 1152 91

Bed rest is an integral part of treatment of numerous diseases. Typical examples are bone fractures of lower extremities and pelvis. Temporary immobilization is necessary also, e.g., in heart diseases (stroke), backbone and imminent abortion. The sick organism spares energy during the bed rest wich is beneficial. However, bed rest results in many alterations which are disadavantageous. They concern the function of almost all organs and systems but affect most significantly the locomotor and ciruclatory systems. Bed rest brings also about changes in the composition of peripheral blood and functions of the morphotic elements of blood. Red blood cells are subjected to the action of large amounts of reactive oxygen species (ROS). During oxidation of hemoglobin to methemoglobin superoxide radical anion (O2-) is formed: HbFe2+ + O2 --> MetHbFe3+ + O2- (1) Ferrous and ferric ions present in the cytoplasm of red blood cells may be catalysts of the Fenton reaction leading to the production of the hydroxyl radical: O2- + Fe3+ --> O2- + Fe2+ (2) Fe2+ + H2O2 --> Fe3+ + OH + HO- (3) OH shows a tremendous reactivity. It may react with lipids, proteins, nucleic acids and carbohydrates. The process of lipid peroxidation is best understood. It concerns mainly polyunsaturated fatty acids present in cell membranes. Peroxidation of membrane lipids decreases membrane fluidity and impairs its barrier function. The lowered membrane fluidity compromises erythrocyte deormability which in turn disturbs oxygen delivery to the tissues. End productions of lipid peroxidation are low-molecular wieght compounds, among them carbohydrates (ethane and pentane) and aldehydes, e.g. malondialdehyde (MDA). MDA concentration is an acknowldeged marker of the intensity of lipid peroxidation. Erythrocytes contain a complex system of protection against the action of ROS. It includes various enzymatic and non-enzymatic mechanism. The most important antioxidative enzymes of the red blood cells are superoxide dismutase (Cu,Zn-SOD, EC 1.15.1.1) catalase (CAT, EC 1.11.1.6) and glutathione peroxidase (GSH-Px, EC 1.11.1.9). Cu,Zn-SOD catalyzes the dismuation of O2- to hydrogen peroxide (H2O2). Catalase and peroxidase remove H2O2 and, moreover, GSH-Px can reduce lipid peroxides. Under normal conditions an equilibrium exists between the formation and removal ROS. If ROS are formed in excess or the defensive antioxidative mechanism are inefficient, oxidative stress develops. Derangement of the equilibrium between the formation and removal of ROS is important in the pathosgenesis of many diseases, e.g. atherosclerosis, diabetes, Down syndrome and Alzheimer disease. There are literature data on disturbances of enzymatic antioxidant defense mechanism of blood plateless during bed rest. This study was aimed at an examination of the post-traumatic bed rest on the enzymatic antioxidative defense mechanisms and lipid peroxidation in erythrocytes.
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PMID:Effect of long term bed rest in men on enzymatic antioxidative defence and lipid peroxidation in erythrocytes. 1154 39

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