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

Vitamin E (alpha-tocopherol) is a potent peroxyl radical scavenger. According to the oxidative theory of atherosclerosis, it prevents oxidation of low-density lipoprotein (LDL) and thereby lowers the risk of cardiovascular disease. It also mediates cell actions, and specifically decreases monocyte superoxide anion-production (O2.--production), which is involved in LDL oxidation. We investigated whether alpha-tocopherol-containing LDL decreases this production in a manner dependent on the LDL alpha-tocopherol content (the alpha-tocopherol/apoB molar ratio) in human, phorbol ester-stimulated, adherent monocytes. We found that O2.--production was inhibited by native LDL (n-LDL) in a manner highly sensitive to the increasing alpha-tocopherol content (range 4.5 8). In addition: (1) inhibition was greater when alpha-tocopherol was associated to acetylated LDL (ac-LDL), the maximal percentage of inhibition being 80% as opposed to 35% for n-LDL; (2) the alpha-tocopherol overloading of either form of LDL did not produce further inhibition; (3) the free form of alpha-tocopherol produced lower inhibition compared with the lipoprotein-associated forms; (4) inhibition was not related to the cell content of alpha-tocopherol. We propose that the cell targeting of alpha-tocopherol is crucial to the inhibition of monocyte O2.--production, and thus that the role of normal LDL-alpha-tocopherol contents (range 6-8) in the prevention of atherogenic processes needs to be reexamined.
Atherosclerosis 1998 Jun
PMID:Monocyte superoxide production is inversely related to normal content of alpha-tocopherol in low-density lipoprotein. 969 Sep 9

Vitamin E acts as an important antioxidant against oxidative modification of low density lipoprotein (LDL) which is accepted as an initial event in the pathogenesis of atherosclerosis. In spite of the numerous studies and reports, the action and role of vitamin E have not been fully elucidated yet. In this brief overview, the dynamics of action of vitamin E as an antioxidant have been discussed and it is emphasized that the total antioxidant potency is determined by the relative importance of many competing reactions which is determined by the reactivities and concentrations of substrates, radicals and antioxidant and by physical factors of the environment.
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PMID:Dynamics of vitamin E action against LDL oxidation. 973 8

Vitamin E was advocated as an effective treatment for heart disease by Dr. Even Shute of London, Ontario more than 50 years ago. His pioneering claims, which were unacceptable to the medical community at large, have been confirmed by recent findings from epidemiologic studies and clinical trials. This review integrates our current knowledge of atherogenesis with the biological functions of vitamin E. The response-to-injury hypothesis explains atherosclerosis as a chronic inflammatory response to injury of the endothelium, which leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components. Inflammatory and other stimuli trigger an overproduction of free radicals, which promote peroxidation of lipids in LDL trapped in the subendothelial space. Products of LDL oxidation are bioactive, and they induce endothelial expression and secretion of cytokines, growth factors and several cell surface adhesion molecules. The last-mentioned are capable of recruiting circulating monocytes and T lymphocytes into the intima where monocytes are differentiated into macrophages, the precursor of foam cells. In response to the growth factors and cytokines, smooth muscle cells proliferate in the intima, resulting in the narrowing of the lumen. Oxidized LDL can also inhibit endothelial production of prostacyclin and nitric oxide, two potent autacoids that are vasodilators and inhibitors of platelet aggregation. Evidence is presented that vitamin E is protective against the development of atherosclerosis. Vitamin E enrichment has been shown to retard LDL oxidation, inhibit the proliferation of smooth muscle cells, inhibit platelet adhesion and aggregation, inhibit the expression and function of adhesion molecules, attenuate the synthesis of leukotrienes and potentiate the release of prostacyclin through up-regulating the expression of cytosolic phospholipase A2 and cyclooxygenase. Collectively, these biological functions of vitamin E may account for its protection against the development of atherosclerosis.
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PMID:Vitamin E and atherosclerosis. 977 22

The pineal hormone, melatonin, was recently found to be a potent free scavenger for hydroxyl and peroxyl radicals. Melatonin also inhibits neuronal and thymocyte damage due to oxidative stress. Atherosclerosis development is mediated by low-density lipoprotein (LDL) oxidation and the endocytosis of oxidized LDL by resident macrophages in the subendothelial vascular wall. Furthermore, the cytotoxic effect of oxidized LDL increases atherogenicity. The goal of this study was to compare the antioxidant activities of melatonin and vitamin E against in vitro LDL oxidation and their cytoprotective actions against oxidized LDL-induced endothelial cell toxicity. An attempt at loading LDL with melatonin by incubating human plasma with an ethanolic melatonin solution gave only low protection against Cu2+-induced LDL oxidation in comparison with vitamin E and gave no detectable incorporation of melatonin into LDL, measured by high-performance liquid chromatography (HPLC) coupled to UV detection. High concentrations of melatonin (10-100 microM) added to the oxidative medium induced a clear inhibition of Cu2+-induced LDL oxidation, characterized as an increase in the lag-phase duration of conjugated diene formation and decreases in the maximal rate of the propagation phase and in the maximal amount of conjugated diene formation. Determination of the median efficacious dose (ED50) of melatonin and vitamin E by their ability to increase lag-phase duration showed that melatonin was less active than vitamin E (ED50, 79 vs. 10 microM, respectively). Melatonin was also less active than vitamin E in limiting the formation of thiobarbituric acid-reactive substances (TBARS) and LDL fluorescence intensity increase in the medium during Cu2+-induced LDL oxidation. Cu2+-induced LDL oxidation in the presence of 100 microM melatonin produced oxidized LDLs that were less recognizable for the scavenger receptors of J774 macrophages than were untreated LDLs. Vitamin E, 10 microM, was more active than 100 microM melatonin in inhibiting LDL oxidation and the resulting lipoprotein alterations leading to binding internalization and degradation by the J774 macrophages. Vitamin E, 100 microM, inhibited the pursuit of the oxidation of oxidized LDL mediated by bovine aortic endothelial cells (BAECs) in a culture medium containing Cu2+, whereas 100 microM melatonin had no antioxidant effect. Melatonin, 100 microM, as well as 100 microM vitamin E inhibited intracellular TBARS formation during the incubation of BAECs with highly oxidized LDL but had no influence on the increase in glutathione (GSH) concentration during this lengthy exposure (16 h) of BAECs to highly oxidized LDL. During this period, the same dose of vitamin E but not of melatonin tended to limit the decrease in adenosine triphosphate (ATP) concentration. Vitamin E, 100 microM, did not significantly reduce cellular lactate dehydrogenase (LDH) release in the culture medium during the incubation of oxidized LDL with BAECs, whereas 100 microM melatonin dramatically increased this release. These data show that melatonin is less active than vitamin E in inhibiting in vitro LDL oxidation and does not inhibit the cytotoxicity of oxidized LDL toward cultured endothelial cells. The concentrations necessary to inhibit LDL oxidation are far beyond those found in human plasma (100 microM vs. 100 pM). Therefore our results indicate that the pineal hormone melatonin per se appears to have little antiatherogenic property in the in vitro oxidation of LDL and the cytoprotective action against the toxicity of oxidized LDL. Nevertheless, in vivo LDL oxidation takes place in the subendothelium of the artery wall, and nothing is known about the concentration of melatonin or its catabolites in this environment.
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PMID:A high concentration of melatonin inhibits in vitro LDL peroxidation but not oxidized LDL toxicity toward cultured endothelial cells. 978 26

One of the earliest steps of atherosclerotic plaque formation is an increase of circulating apolipoprotein B-containing lipoproteins which, after infiltrating the subendothelial space, undergo oxidative modification. Fenofibrate is an effective cholesterol- and triglyceride-lowering agent which has been shown to be beneficial in the treatment of atherosclerosis. Vitamin E, or alpha-tocopherol, is a powerful antioxidant which has been shown in a variety of studies to prevent lipoprotein peroxidation. The purpose of the present study was to investigate the effect of fenofibrate treatment, either alone or in combination with alpha-tocopherol, in reducing the susceptibility of lipoproteins to oxidative modification. Rats fed a normal diet were treated for up to 27 d with fenofibrate, either alone or in combination with equimolar doses of alpha-tocopherol. Combined VLDL (very low density lipoproteins) and LDL (low density lipoproteins) isolated after fenofibrate treatment were more resistant to copper-mediated oxidation, as assessed by conjugated diene formation. Lag time was prolonged up to 3.2-fold, while the maximal rate of diene production was significantly decreased by up to 2.2-fold. Treatment of rats with alpha-tocopherol alone at the selected dose had no significant effect on lag time, while the propagation rate was slightly decreased. Coadministration of fenofibrate with alpha-tocopherol prolonged the lag phase to a greater extent than fenofibrate alone, showing a synergistic interaction between the two compounds. Finally, the combination of fenofibrate and alpha-tocopherol was significantly more effective in modifying lipoprotein oxidation parameters than what was observed with alpha-tocopherol and bezafibrate or gemfibrozil. Thus, in addition to its well-established effects on lipoprotein concentrations and atherogenic parameters, fenofibrate reduces the susceptibility of VLDL and LDL to oxidative modification and exerts its action synergistically with alpha-tocopherol.
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PMID:Fenofibrate protects lipoproteins from lipid peroxidation: synergistic interaction with alpha-tocopherol. 1038 Jan 22

The oxidative modification of low-density lipoprotein (LDL) plays an important role in atherosclerosis. Protecting LDL from oxidation has been shown to reduce the risk of coronary heart disease. In this study, we compared the protective effects of two lipophilic antioxidants (vitamin E and lazaroid) with two hydrophilic antioxidants (trolox and vitamin C) in the presence of several different free radical generating systems. Vitamin E (IC50 = 5.9 microM) and lazaroid (IC50 = 5.0 microM) were more effective in inhibiting lipid peroxidation caused by a Fe-ADP free radical generating system than vitamin C (IC50 = 5.2 x 10(3) microM) and trolox (IC5 = 1.2 x 10(3) microM). Preincubation of lipoproteins with a lipophilic antioxidant increased the protective effect against various free radicals. Preincubation with hydrophilic antioxidants did not have an effect. We also tested the efficacy of the antioxidants when the free radicals were generated within the lipid or the aqueous environment surrounding the LDL. For this purpose, we used the peroxyl generating azo-compounds AMVN (2,2'-azobis(2,4-dimethylvaleronitrile)) and AAPH (2,2'azobis(2-amidinopropane) dihydrochloride). All of the antioxidants tested were more effective against free radicals generated in a water soluble medium than they were against free radicals generated in a lipid environment. In conclusion, our data demonstrate that lipid solubility is an important factor for both the antioxidant and the free radical generating systems in determining the extent of lipid peroxidation in LDL. Our data also demonstrate that antioxidant efficacy in one set of experimental conditions may not necessarily translate into a similar degree of protection in another set of conditions where lipophilicity is a variable.
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PMID:The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation. 1040 18

The role of vitamin E on the anti-atherosclerotic effect of fish oil in diet-induced hypercholesterolemic rabbits was studied in male New Zealand white rabbits. The animals were randomly divided into six groups of 14 each according to the chow given them. Group I, control, rabbits were fed regular laboratory rabbit chow. In addition to the regular chow, Group II rabbits were fed a high (1%) cholesterol-enriched diet. Group III had the same diet as Group II plus 450 mg vitamin E/1000 g chow. Group IV also had the same diet as Group II plus 10% fish oil, but without vitamin E. Group V's diet contained 1% cholesterol, 10% fish oil, and 450 mg vitamin E/1000 g chow. Group VI had the same diet as Group V, but with 150 mg vitamin E/1000 g chow. At the end of a 6-week feeding, the ascending aorta from seven rabbits from each group was harvested for the analysis of prostanoid production, thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity, and cholesterol and vitamin E levels; the same tissue from the other seven rabbits from each group was obtained for the delineation of atherosclerotic lesions by planimetry after the Sudan IV stain. The high cholesterol diet-treated rabbits had worse prostanoid synthesis and higher TBARS levels, which paralleled the severity of the atherosclerosis. Vitamin E or fish oil supplementation in a high cholesterol diet had beneficial prostanoid production, reduced aortic TBARS levels, and attenuated atherosclerotic lesions; these effects were potentiated when vitamin E and fish oil were combined together. The atherosclerotic lesion reduction in rabbits treated with high cholesterol plus fish oil and 450 mg vitamin E/1000 g chow reached statistical significance (P < 0.05) compared to high cholesterol and the same dose of vitamin E-treated rabbits. The rabbits treated with high cholesterol plus fish oil, but without vitamin E or with 150 mg vitamin E/1000 g chow showed an increased plasma creatine kinase activity at 4 (P < 0.01 and 0.05, respectively) and 6 (P < 0.001 and 0.01, respectively) week of feeding. These results suggest that vitamin E and/or fish oil attenuate atherosclerosis in high cholesterol-fed rabbits; vitamin E and fish oil potentiated the effect of each other. Furthermore, without sufficient vitamin E supplementation, rabbits treated with high cholesterol plus fish oil will show an elevation of plasma creatine kinase activity.
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PMID:The role of vitamin E on the anti-atherosclerotic effect of fish oil in diet-induced hypercholesterolemic rabbits. 1041 Mar 81

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.
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PMID:Nutrition and dietary supplements. 1051 85

The changes in low density lipoprotein (LDL) composition and oxidizability after LDL-apheresis (LA) using dextran sulfate cellulose columns were evaluated in 12 hypercholesterolemic men (mean+/-S.D. total cholesterol (TC) 9.7+/-1.8 mmol/l). After 10-20 months on biweekly LA combined with simvastatin 40 mg per day immediate pre-apheresis levels of TC, LDL-cholesterol, and apolipoprotein B were decreased to 5.3+/-1.3 mmol/l, 3.3+/-1.2 mmol/l, and 1.6+/-0.4 g/l, respectively, whereas apheresis induced mean acute reductions of 61, 78, and 76%, respectively. Measurements of copper-induced LDL-oxidizability in vitro showed an increased resistance against oxidation after LA until day 3 post-treatment: lag time (min) (day 0 (before LA) versus day 1 (post-LA)) 112+/-27 versus 130+/-26 (P=0.001), maximal rate of diene production (nmol/min per mg LDL) 11.1+/-2.7 versus 9.1+/-2.1 (P=0.001), and time to maximal diene production (min) 186+/-39 versus 209+/-35 (P=0. 001). Analysis of the chemical composition of LDL revealed a 25% (P<0.001) reduced content of cholesteryl esters and a decrease of the cholesterol to protein ratio of 1.20+/-0.25 to 0.70+/-0.22 (P<0. 001) through the 3rd day post-LA. Linoleic acid and arachidonic acid content of LDL decreased 11 and 18%, respectively, at the expense of palmitic acid. Vitamin E levels (mg/l) were significantly lowered due to reduction of the lipoprotein pool by apheresis; however, vitamin E content of LDL did not change in the days after apheresis when expressed per g protein or per micromol linoleic acid. The changes in fatty acid pattern were strongly associated with changes in LDL-oxidizability indices (P</=0.01). Thus, LA effectively decreased LDL pool size, inducing the presence of less buoyant lipoproteins, which were less susceptible to in vitro oxidation. This was not explained by changes in vitamin E levels, but by short-term changes in the fatty acids composition.
Atherosclerosis 1999 Nov 01
PMID:The rebound of lipoproteins after LDL-apheresis. Effects on chemical composition and LDL-oxidizability. 1052 31

Atherosclerotic lesions can be characterized as accumulation of cholesterol esters and pathologic reactions by various cell groups. The pathogenesis of atherosclerosis has been discussed primarily on the basis of these two phenomena. A well-known concept to explain the etiology of atherosclerosis is the theory of response to injury. According to this theory, physiologically active substances such as platelet-derived growth factor (PDGF) and macrophage colony-stimulating factor (M-CSF) are released in response to injury of the vascular wall, and these substances induce pathologic reactions by the cells constituting the vascular wall. In the presence of excessive amounts of low-density lipoprotein (LDL), denatured LDL modified by oxidation or other reactions on the vascular wall is taken up by macrophages via scavenger receptors, resulting in the formation of foam cells and accumulation of cholesterol esters. Vitamins including Vitamin C and Vitamin E may play an important role in form cell formation by preventing the oxidation.
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PMID:[Atherosclerosis]. 1054 Aug 84


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