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)

The incidence of atherosclerosis increases with age, as do various indices of free-radical mediated damage, e.g., lipid peroxidation. Because lipid peroxidation plays a prominent role in lipoprotein oxidation, likely a prelude to atherosclerosis, we compared the susceptibility of lipoproteins to oxidation in young (19-30 years) and elderly (59-86 years) groups. Although we found no significant differences in serum malondialdehyde (MDA) or oxidized LDL antibodies (OLAB) between young and elderly lipoproteins, MDA was directly related to OLAB regardless of age (r = 0.322, p = 0.005) and there was a trend for lower OLAB levels (30.5%, p = 0.079) in the elderly compared to the young population. Overall, serum antioxidant status was either similar or greater in the elderly group compared to the young group, likely reflecting antioxidant supplementation by the elderly group. OLAB was inversely related to Vitamin C (r = -0.310, p = 0.008) and Vitamin E intake (r = -0.277, p = 0.018) from foods and supplements. Serum levels of Vitamin C and Vitamin E were significantly higher (18.5%, p = 0.021 and 58.1 %, p < 0.001, respectively) in the elderly group compared to the young group and the ratio of Vitamin E to Vitamin C was significantly higher (30.4%, p = 0.042) in the serum of the elderly group. Oxidation of serum LDL and antioxidant status were not affected by age; however, the ratio of serum Vitamin E to Vitamin C was higher in the elderly group which may affect Vitamin E recycling.
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PMID:Oxidation of serum low-density lipoprotein (LDL) and antioxidant status in young and elderly humans. 1621 44

Inappropriate response of the carotid body region to encroachment of its perfusion results in essential hypertension (EH) and/or non-insulin dependent diabetes mellitus (NIDDM). This encroachment is caused by atherosclerosis. The carotid body perceives the encroachment on the lumen as a reduction in the availability of oxygen and glucose for the brain. Raising the perfusion pressure (thus, resulting in EH) and/ or inducing insulin resistance (causing NIDDM) are seen as compensatory mechanisms in response to the primary pathology, ie the encroachment of the lumen by atherosclerosis. Therefore, the reduction or reversal of the atherosclerosis process will help improve perfusion to the carotid bodies, which will in turn reduce or reverse the pathophysiological compensatory adjustments described above. A supplemental therapy, in addition to the standard treatment, with vitamin C is suggested here. The argument in favour of this suggestion is the basis of this paper. Vitamin C is a very important antioxidant. It is suggested to be used without any interference with the usual therapy prescribed for these two chronic diseases. It is recommended to be administered in small, frequent doses of 100mg every 2h, except during sleep. There is no need for compensation for the occasional missed dose. The safety of larger doses of vitamin C than the current recommendations, represents the beauty and is reassuring in recommending this approach.
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PMID:Treatment of essential hypertension and non-insulin dependent diabetes mellitus with vitamin C. 1709 41

Oxidative stress and oxidative damage to tissues are common end points of chronic diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. The aim of the present study was to evaluate the possible protective effects of Murraya koenigii leaves extract against beta-cell damage and antioxidant defense systems of plasma and pancreas in streptozotocin induced diabetes in rats. The levels of glucose and glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E, ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system such as the level of reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of M. koenigii leaves extract. Transmission electron microscopic studies also revealed the protective nature of M. koenigii leaves on pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract was compared with glibenclamide, a well-known hypoglycemic drug.
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PMID:Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic beta-cells in experimental diabetes in rats. 1718 70

The effect of oral administration of vitamin C on serum lipids and electrolyte profile were investigated in albino rats of the Wistar strain. Eighteen (18) albino rats of opposite sexes weighing between 150-300 g were used for the study and randomly assigned on the basis of body weight and litter origin to three study groups of six animals each. The control group received via oral route a placebo (4 ml of distilled water), while test groups 1 and II received 100 mg/kg body weight and 200 mg/kg body weight of vitamin C in 2.5 ml and 5.0 ml of the vehicle via gastric intubation respectively. The administration of vitamin C for 30 days produced a significant [P < 0.05] decrease in total cholesterol (TC), very low-density lipoprotein (VLDL) and low density lipoprotein (LDL) in the test groups versus control but there was no change in triglycerides (TG) and High density lipoprotein (HDL) levels. Computed HDL:LDL ratio also increased in the treatments relative to the control. Except for computed HDL:LDL ratio all the other changes were dose dependent and there was a slight non-significant increase in all electrolytes (Na(+), K(+); and HCO3(-) ions. The study confirms the hypocholesterolaemic effect of vitamin C and that Vitamin C has no adverse effect on serum electrolytes. It is suggested that its administration in moderate to high doses may protect against atherosclerosis and hypertension.
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PMID:Effect of vitamin C on serum lipids and electrolyte profile of albino Wistar rats. 1724 28

Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype-related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.
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PMID:Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. 1764 91

Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.
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PMID:Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid. 1766 49

Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied "too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis.
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PMID:Inflammation in the vascular bed: importance of vitamin C. 1858 47

Increased oxidative/nitrosative stress, resulting from generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) appears to play an important role in the inflammatory responses to atherosclerosis. By using MitoTracker Orange CM-H(2)TMRos, CM-H(2)DCFDA (DCF-DA), Dihydrorhodamine 123 (DHR123), DAF-FM, Dihydroethidium (DHE) and JC-1 alone or in all combinations of red and green probes, the present study was designed to monitor the ROS and RNS generation in acute exposure of single monocyte U937-derived macrophage to oxidized low density lipoprotein (Ox-LDL). Acute Ox-LDL (100 microg/ml) treatment increased time-dependently production of intracellular nitric oxide (NO), superoxide (O2*-), hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONOO(-)), and decreased mitochondrial membrane potential (Deltapsi) in single cell. Pretreatment of aminoguanidine (an inhibitor of inducible nitric oxide synthase (iNOS), 10 microM) and vitamin C (an antioxidant agent, 100 microM) for 2h, reduced significantly the Ox-LDL-induced increase of NO and O2*-, and vitamin C completely inhibited increase of intracellular NO and O2*-. In contrast to aminoguanidine, Vitamin C pretreatment significantly prevented Ox-LDL-induced overproduction of NO and O2*- (P<0.01), indicating that antioxidant may be more effective in therapeutic application than iNOS inhibitor in dysfunction of ROS/RNS. By demonstrating a complex imbalance of ROS/RNS via fluorescent probes in acute exposure of single cell to Ox-LDL, oxidative/nitrosative stress might be more detected in the early atherosclerotic lesions.
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PMID:Dynamic determination of Ox-LDL-induced oxidative/nitrosative stress in single macrophage by using fluorescent probes. 1878 27

To assess whether ascorbic acid decreases the cytotoxicity of oxidized human low density lipoprotein (oxLDL) in cells involved in atherosclerosis, its interaction with oxLDL was studied in murine RAW264.7 macrophages. Macrophages took up ascorbate to millimolar intracellular concentrations and retained it with little loss over 18h in culture. Culture of the macrophages with oxLDL enhanced ascorbate uptake. This was associated with increased expression of the ascorbate transporter (SVCT2), which was prevented by ascorbate and by inhibiting the NF-kappaB pathway. Culture of RAW264.7 macrophages with oxLDL increased intracellular dihydrofluorescein oxidation and lipid peroxidation, both of which were decreased by intracellular ascorbate. Ascorbate also protected the cells against oxLDL-induced cytotoxicity and apoptosis, but it did not affect macrophage accumulation of lipid from oxLDL or oxLDL-induced increases in macrophage cytokine secretion. These results suggest that ascorbate protects macrophages against oxLDL-induced oxidant stress and subsequent apoptotic death without impairing their function.
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PMID:Oxidized lipoprotein induces the macrophage ascorbate transporter (SVCT2): protection by intracellular ascorbate against oxidant stress and apoptosis. 1925 85

Myeloperoxidase (MPO) is a heme enzyme, released by activated leukocytes at sites of inflammation, which catalyzes the formation of the potent oxidant, hypochlorous acid (HOCl), from H2O2. HOCl is a key component of the inflammatory response and is bactericidal but has been linked with several human pathologies as a result of damage to host tissue. Elevated plasma MPO levels are a strong independent risk factor, and predictor of outcomes, for cardiovascular disease. Rate constants for reaction of HOCl with individual biological targets and the products of these reactions have been determined, but the targets of HOCl in complex biological fluids such as plasma are incompletely defined. In this study, rate constants (M(-1) s(-1)) for the reactions of ascorbate with HOCl (ca. 6 x 10(6)) and imidazole chloramine (7.7 x 10(4)) have been determined to supplement known kinetic parameters. HOCl-mediated oxidation of the major plasma protein, albumin, was investigated both experimentally and computationally; these approaches provide consistent data. The computational studies were extended to examine the fate of HOCl in plasma. The model predicts that plasma proteins consume the majority of HOCl with limited damage to other materials. Ascorbate or alpha-tocopherol, even at the levels achieved in human supplementation studies, do not attenuate these reactions. In contrast, elevated levels of thiocyanate ions (SCN(-)), as detected in heavy smokers, can modulate HOCl-mediated reactions as a result of the formation of the highly specific oxidant hypothiocyanous acid (HOSCN). These observations support the hypothesis that MPO-generated HOSCN is a key agent in smoking-enhanced atherosclerosis.
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PMID:What are the plasma targets of the oxidant hypochlorous acid? A kinetic modeling approach. 1932 2


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