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 most commonly known function of vitamin E in vivo is the prevention of undue oxidation of polyunsaturated fatty acids. It has been claimed that in vitamin E deficiency, the arachindonic content of the tissue increases as does the content of higher unsaturated fatty acid. In experimental chronic ozone intoxication, vitamin E was shown to protect against ozone poisoning. There was no evidence however that a rapid turnover of fatty acids occurred during ozone exposure. A possibility is that the increased tissue content of higher polyunsaturated fatty acids is due to the arrest of their further metabolization through lack of vitamin E. The higher polyunsaturated fatty acids are synthesized from linoleic and linolenic acids; in turn, the unsaturated fatty acids with 3 or more double bonds are the basic compounds of prostaglandins. Important functions of prostaglandins include: prevention of blood platelet aggregation; blood vessel dilatation; lowering of blood pressure; stimulation of smooth muscle; and inhibition of fat mobilization by noradrenaline. Diminished activity of one or more of the prostaglandins may be a promoting factor for atherosclerosis and its complication, especially myocardial infarction. These diseases may be prevented by increasing daily consumption of polyunsaturated fatty acids, mainly linoleic acid which can be derived from vegetable oils.
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PMID:Ozone, vitamin E, fatty acids, prostaglandins, atherosclerosis and its complications. 470 14

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater).
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PMID:Vitamin E in humans: demand and delivery. 883 30

Various lipoxygenases (LO) oxidize low density lipoprotein (LDL) in vitro and 15-LO has been implicated in the development of atherosclerosis in vivo. Direct oxidation of phospholipids (PL) and cholesteryl esters (CE) by LO has been proposed as a mechanism whereby these enzymes cause or contribute to LDL lipid peroxidation. Herein we show that the extent to which recombinant human 15-LO (rhLO) caused peroxidation of LDL's esterified core and surface lipids depended on, and directly related to, the alpha-tocopherol (alpha-TOH) content of the lipoprotein. Thus, CE and PL of in vivo alpha-TOH-depleted LDL, isolated from a patient with familial isolated vitamin E deficiency, were resistant to oxidation by rhLO, whereas those in alpha-TOH-containing LDL from the same patient receiving vitamin E supplements readily oxidized. The extent to which rhLO caused oxidation of CE and PL directly and linearly correlated with LDL's content of vitamin E, as demonstrated by studies with in vitro alpha-TOH-depleted lipoproteins. The geometric isomers of oxidized cholesteryl linoleate formed in LDL during oxidation initiated by rhLO, matched those obtained during non-enzymic, peroxyl radical-initiated oxidation of LDL whilst alpha-TOH was present. Ascorbate, an efficient co-antioxidant for alpha-TOH, completely prevented rhLO-initiated oxidation of LDL's CE, but did not inhibit rhLO-mediated oxidation of unesterified linoleate. These results are inconsistent with direct oxidation of LDL esterified lipids by rhLO. Isolated LDL contained free fatty acids (FFA), and its exposure to rhLO caused a rapid formation of linoleate hydroperoxide. To reconcile these data, we propose that during rhLO-initiated oxidation of LDL, enzymic oxidation of FFA preceeds the oxidation of CE and PL, which occurs largely via a tocopherol-dependent process.
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PMID:Oxidation of LDL by recombinant human 15-lipoxygenase: evidence for alpha-tocopherol-dependent oxidation of esterified core and surface lipids. 901 16

Atherosclerosis is characterised by a wide range of clinical manifestations. Hypercholesterolaemia is an independent risk factor for coronary heart disease, the correction of which with statins decreases the incidence of ischaemic events. Hypertension is a major risk for strokes. Prevention of coronary events by an action on the sole arterial blood pressure has been difficult to establish. Tobacco consumption is mainly involved in the risk of lower-limb arterial disease. Diabetes is a major and global enhancer of cardiovascular disease. Assessment of the other "emerging" risk factors (such as vitamin E deficiency, homocysteine, or the type of alcohol consumed) is still in progress. The level of classical risk factors only accounts for the variations between populations that are observed in the United States and in the Northern European countries.
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PMID:[Epidemiology of atherosclerosis: risks and paradoxes]. 1064 43

It has been widely noted that vitamin E shows numerous beneficial effects through and beyond its antioxidative properties; consequently, vitamin E is expected to prevent degenerative diseases. In the field of sports medicine, many studies dealing with vitamin E have been conducted originally from the point of view of its effects on physical performance. Although some earlier studies indicated that vitamin E supplementation could improve physical performance, defects in the study design or statistical analysis were pointed out at a later time. The majority of subsequent well controlled studies have reported no significant effect on physical performance from vitamin E supplementation. Recent studies suggest that endurance exercise may promote free radical generation in the body, and vitamin E may play an important role in preventing the free radical damage associated with endurance exercise. Although there is evidence of free radical involvement in exercise-induced muscle injury, vitamin E supplementation might not be expected to prevent muscle damage caused by exercise in humans without a vitamin E deficiency. Since it is still unclear whether exercise induces lipid peroxidation in the human body, the beneficial effect of vitamin E supplementation on exercise-induced lipid peroxidation has not yet been established. However, it is proposed that as a result of exercise vitamin E may be mobilised from store tissues and redistributed in the body to prevent oxidative damage. Therefore, we are convinced that vitamin E contributes to preventing exercise-induced lipid peroxidation. It has also been indicated that strenuous endurance exercise may enhance the production of oxidised low density lipoprotein (LDL), which plays a key role in the initiation and progression of atherosclerosis. It is also suggested that this enhanced production of oxidised LDL could be reduced if a higher vitamin E status is maintained. Supplementation with 100 to 200mg of vitamin E daily can be recommended for all endurance athletes to prevent exercise-induced oxidative damage and to reap the full health benefits of exercise.
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PMID:Vitamin E supplementation and endurance exercise: are there benefits? 1070 11

Alpha-tocopherol plays an important role as a lipid-soluble antioxidant. It is present in all major mammalian cell types and shows tissue-specific distribution. This suggests the presence of specific proteins involved in intracellular distribution or metabolism of alpha-tocopherol. A diminution of tocopherol plasma concentrations contributes to the development of diseases such as vitamin E deficiency (AVED), atherosclerosis, and prostate cancer. Further evidence has been obtained for the existence of sites in cellular metabolism and signal transduction where alpha-tocopherol potentially plays a regulatory role. A signal transduction modulation specific for alpha-tocopherol has been described in several model systems. Using radioactively labeled alpha-tocopherol as tracer, we have isolated a new alpha-tocopherol-associated protein (TAP) from bovine liver. This protein has a molecular mass of 46 kDa and an isoelectric point of 8.1. From its partial amino acid sequence, a human gene has been identified with high homology to the newly described protein. Sequence analysis has established that the new TAP has structural motifs suggesting its belonging to a family of hydrophobic ligand-binding proteins (RALBP, CRALBP, alpha-TTP, SEC 14, PTN 9, RSEC 45). Human TAP has been cloned into Escherichia coli, and its tissue-specific expression has been assessed by Northern blot analysis.
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PMID:Identification of a novel cytosolic tocopherol-binding protein: structure, specificity, and tissue distribution. 1079 15

Oxidatively modified phospholipids with fragmented acyl chains have attracted much interest because of their proinflammatory activity and their potential involvement in atherosclerosis. They can be formed in vitro by free radical treatment of unsaturated phospholipids but it is not known under which conditions they accumulate in vivo. We assayed one species of fragmented phosphatidylcholine (PC) in human blood plasma by high performance liquid chromatography after precolumn derivatization with chloromethylanthracene. Structural analysis suggested that fragmented PC was a diacyl species with a palmitoyl group and a short oxidized residue, which most likely had four carbons. The concentration of fragmented PC was higher in elderly individuals with coronary heart disease than in young healthy controls. Smoking one cigarette acutely increased the concentration of fragmented PC in healthy adults. Fragmented PC also increased in the reperfusion period after treatment with cardiopulmonary bypass. The increase coincided with a surge of circulating neutrophils. In rats, the plasma concentration of fragmented PC was elevated by vitamin E deficiency and exposure to high oxygen. The data demonstrate that fragmented PC increases in blood plasma in response to various forms of oxidative stress.
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PMID:Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress. 1088 97

Lipoproteins modified by oxidation, glycation, alkylation, and nitration are generated by oxidative stress during inflammation, diabetes, and inadequate supply of dietary antioxidants. A family of genes, the scavenger receptors, recognizes and internalizes modified lipoproteins, making them susceptible to degradation. Clearance of modified lipoproteins by scavenger receptors occurs mainly in macrophages, dendritic cells, and Kupffer cells of the liver. However, scavenger receptor expression also occurs in other cells, such as endothelial cells, aortic smooth muscle cells, neuronal cells, and keratinocytes. Thus, the local clearance of oxidized low-density lipoprotein and the resolution of inflammatory processes may rely in part on the expression of scavenger receptors in "nonprofessional" phagocytes. Uptake of oxidized low-density lipoprotein, without an efficient machinery to degrade them and uncontrolled expression of scavenger receptors, may lead to cellular deregulation, apoptosis, and formation of foam cells. Diseases accompanied by oxidation of lipoproteins, such as atherosclerosis, Alzheimer disease, glomerulosclerosis, ataxia with vitamin E deficiency, and possibly age-dependent lipofuscin deposition, may share a common pathogenetic feature. This review will focus on foam cell formation, mainly within the atherosclerotic lesion, and the possible involvement of aberrant regulation of the scavenger receptor genes. To date, the regulatory mechanisms at the basis of scavenger receptor gene expression and their roles in atherosclerosis and other diseases are not well established. Knowledge on this subject could lead to a better understanding of the pathogenesis, prevention, and therapy of these diseases.
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PMID:Scavenger receptors and modified lipoproteins: fatal attractions? 1090 71

Although lipid peroxidation in the subendothelial space has been hypothesized to play a central role in atherogenesis, the role of vitamin E in preventing lipid peroxidation and lesion development remains uncertain. Here we show that in atherosclerosis-susceptible apolipoprotein E knockout mice, vitamin E deficiency caused by disruption of the alpha-tocopherol transfer protein gene (Ttpa) increased the severity of atherosclerotic lesions in the proximal aorta. The increase was associated with increased levels of isoprostanes, a marker of lipid peroxidation, in aortic tissue. These results show that vitamin E deficiency promotes atherosclerosis in a susceptible setting and support the hypothesis that lipid peroxidation contributes to lesion development. Ttpa(-/-) mice are a genetic model of vitamin E deficiency and should be valuable for studying other diseases in which oxidative stress is thought to play a role.
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PMID:Increased atherosclerosis in hyperlipidemic mice deficient in alpha -tocopherol transfer protein and vitamin E. 1109 17

Since the discovery of vitamin E in 1922, its deficiency has been associated with various disorders, particularly atherosclerosis, ischemic heart disease, and the development of different types of cancer. A neurological syndrome associated with vitamin E deficiency resembling Friedreich ataxia has also been described. Whereas epidemiological studies have indicated the role of vitamin E in preventing the progression of atherosclerosis and cancer, intervention trials have produced contradictory results, indicating strong protection in some cases and no significant effect in others. Although it is commonly believed that phenolic compounds like vitamin E exert only a protective role against free radical damage, antioxidant molecules can exert other biological functions. For instance, the antioxidant activity of 17-beta-estradiol is not related to its role in determining secondary sexual characters, and the antioxidant capacity of all-trans-retinal is distinguished from its role in rhodopsin and vision. Thus, it is not unusual that alpha-tocopherol (the most active form of vitamin E) has properties independent of its antioxidant/radical scavenging ability. The Roman god Janus, shown in ancient coins as having two faces in one body, inspired the designation of 'Janus molecules' for these substances. The new biochemical face of vitamin E was first described in 1991, with an inhibitory effect on cell proliferation and protein kinase C activity. After a decade, this nonantioxidant role of vitamin E is well established, as confirmed by authoritative studies of signal transduction and gene regulation. More recently, a tocopherol binding protein with possible receptor function has been discovered. Despite such important developments in understanding the molecular mechanism and the targets of vitamin E, its new Janus face is not fully elucidated. Greater knowledge of the molecular events related to vitamin E will help in selecting the parameters for clinical intervention studies such as population type, dose response effects, and possible synergism with other compounds.
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PMID:Vitamin E: protective role of a Janus molecule. 1168 57


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