Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological and clinical studies indicate that vitamin E may reduce the risk of cardiovascular disease (CVD). Modulation of adhesion molecule expression and chemokine production by vitamin E may contribute to its beneficial effect. In this study we found that the enrichment of confluent human aortic endothelial cells (HAEC) or U937 monocytic cells with increasing doses of vitamin E (d-alpha-tocopherol, 20, 40, and 60 micromol/l for 20 h) inhibited their adhesion when either or both cell types were stimulated with interleukin (IL)-1beta. Enrichment of HAEC with the same doses of vitamin E suppressed IL-1beta-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin). Supplementation with increasing doses of vitamin E up to 60 micromol/l was not effective in preventing spontaneous production of monocyte chemoattractant protein-1 (MCP-1), but supplementation with vitamin E at 60 micromol/l reduced IL-8 production significantly. However, IL-1beta-induced productions of both MCP-1 and IL-8 were dose-dependently suppressed by enrichment of cells with vitamin E. Vitamin E, at the doses used, did not significantly change the spontaneous production but dose-dependently inhibited the IL-1beta-induced production of inflammatory cytokine IL-6. We concluded that vitamin E could inhibit production of chemokines and inflammatory cytokines, in addition to inhibiting adhesion of HAEC to monocytes by reducing expression of adhesion molecules when cells were activated with an inflammatory cytokine. These mediators are actively involved in the pathogenesis of atherosclerosis. Therefore, their inhibition by vitamin E may contribute to vitamin E's reported reduction in risk of CVD.
Atherosclerosis 1999 Dec
PMID:Effect of vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes. 1055 16

A review is presented of studies on the effects of vitamin E on heart disease, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellular, and animal studies, which are impressive both in quantity and quality, leave no doubt that vitamin E, the most important fat-soluble antioxidant, protects animals against a variety of types of oxidative stress. The hypothesis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) particle initiates a complex sequence of events that leads to the development of atherosclerotic plaque. This hypothesis is supported by numerous studies in vitro, in animals, and in humans. There is some evidence that the ex vivo oxidizability of a subject's LDL is predictive of future heart events. This background in basic science and observational studies, coupled with the safety of vitamin E, led to the initiation of clinical intervention trials. The three trials that have been reported in detail are, on balance, supportive of the proposal that supplemental vitamin E can reduce the risk for heart disease, and the fourth trial, which has just been reported, showed small, but not statistically significant, benefits. Subgroup analyses of cohorts from the older three trials, as well as evidence from smaller trials, indicate that vitamin E provides protection against a number of medical conditions, including some that are indicative of atherosclerosis (such as intermittent claudication). Vitamin E supplementation also produces an improvement in the immune system and protection against diseases other than cardiovascular disease (such as prostate cancer). Vitamin E at the supplemental levels being used in the current trials, 100 to 800 IU/d, is safe, and there is little likelihood that increased risk will be found for those taking supplements. About one half of American cardiologists take supplemental vitamin E, about the same number as take aspirin. In fact, one study suggests that aspirin plus vitamin E is more effective than aspirin alone. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is "complete." At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.
 ...
PMID:Vitamin E and heart disease: basic science to clinical intervention trials. 1065

Vitamin E, the major lipid soluble plasma antioxidant, has been reported to be reduced in patients with coronary atherosclerosis. We have measured the levels of plasma alpha-tocopherol (the predominant form of plasma vitamin E) in 128 patients with different reported degrees of angina. Patients with mild to moderate angina (grades I or II (CSS score)) (n = 64), and patients with severe angina (grades III and IV) (n = 64) were recruited from Cardiology Clinics in the U. K. Healthy controls (n = 33) and patients with hyperlipidaemia (n = 28) were also recruited. The groups of patients with angina did not differ significantly for mean age (58 +/- 1.0 years vs. 59 +/- 1.0 years, respectively); sex distribution (the M:F ratio was 48 : 16 and 46 : 18 for the respective groups); or prevalence of smoking (12% vs. 9%), or hypertension (19% vs. 33%). Total cholesterol levels were higher in the group with severe angina (5.9 +/- 0.16 mmol/l vs. 5.3 +/- 0.13 mmol/l P < 0.05). Absolute levels of plasma vitamin E were not significantly different between the angina subgroups (12.9 +/- 0.40 mg/l for the mild-moderate angina group vs. 12.5 +/- 0.51 mg/l for the severely affected group), but were positively correlated with plasma cholesterol concentrations in each case (P < 0.001). The ratio between plasma vitamin E: total cholesterol was significantly lower in the patients with severe angina (mean 2.20 +/- 0.09 mg/mmol) vs. a mean value of 2.46 +/- 0. 08 mg/m mol in the mildly affected group (P < 0.05). The plasma vitamin E: total cholesterol ratio in patients with severe angina was also significantly lower (P < 0.05) compared to either healthy controls with comparable total cholesterol levels (n = 33), or hypercholesterolaemic subjects (n = 28) without symptomatic coronary disease (mean ratios were 2.69 +/- 0.40 mg/mmol and 2.74 +/- 0.68 mg/mmol, respectively). Vitamin E has previously been demonstrated to protect endothelial function in the presence of hypercholesterolaemia, possibly by preserving nitric oxide bio-activity. It also inhibits LDL oxidation. Hence, a high plasma vitamin E: total cholesterol ratio may be associated with an amelioration of angina.
 ...
PMID:Cholesterol standardized plasma vitamin E levels are reduced in patients with severe angina pectoris. 1071 65

Diabetes mellitus is associated with an increased risk of premature atherosclerosis, which may be due in part to an increased rate of low density lipoprotein (LDL) oxidation. Previous studies have shown that vitamin E, probucol, and lovastatin can reduce the oxidative susceptibility of LDL in normoglycemic animal models; however, few studies have investigated this in conjunction with aortic fatty streak lesion formation in diabetic hyperlipidemic models. Forty-eight Syrian hamsters were made diabetic by intraperitoneal injection of low dose streptozotocin. Diabetic animals (12 animals/groups) received a high saturated fat and cholesterol diet for 12.5 weeks. At 2.5 week of dietary treatments, the diet was supplemented with either: (1) 500 IU/day vitamin E (D+E); (2) 1% probucol w/w of the diet (D+P); (3) 25 mg/kg lovastatin (D+L); or (4) diabetic control (D). An age-matched group of hamsters (n=6) receiving the same diet but not made diabetic (ND) was used as control. At the end of the study, aortic arch foam cell-rich fatty streak lesion, plasma glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), phospholipids, alpha-tocopherol, plasma lipid peroxide and the susceptibility of LDL to copper-catalyzed oxidation were determined. Diabetes increased plasma glucose, and when combined with an atherogenic diet resulted in a further increase of plasma lipids. Vitamin E, probucol, and lovastatin significantly reduced plasma TG in the diabetic hamsters fed the atherogenic diet. Vitamin E treatment increased TC, probucol reduced HDL-C without affecting TC; whereas lovastatin reduced TC and selectively decreased non-HDL-C, and significantly reduced fatty streak lesion formation in the aortic arch. While vitamin E and probucol were effective in reducing several indices of oxidative stress including plasma lipid peroxides, cholesterol oxidation products and in vitro LDL oxidation, they had no effect on fatty streak lesion formation. Our results indicate that the LDL in diabetic animals is more susceptible to oxidation than in non-diabetic hamsters and that not only vitamin E and probucol but also lovastatin provide antioxidant protection. It appears that in this combined model of diabetes and hypercholesterolemia, progression of fatty streak lesion formation is mainly associated with changes in TC and non-HDL-C as affected by lovastatin, and is less dependent on the extent of LDL oxidation, changes in plasma TG level and oxidative stress status.
Atherosclerosis 2000 Apr
PMID:The effect of vitamin E, probucol, and lovastatin on oxidative status and aortic fatty lesions in hyperlipidemic-diabetic hamsters. 1072 77

There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu(2+) was increased by 157% (110-232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185-259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122-192%) (P<0.005) and 177% (101-267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115-169%) (P<0.005) and 171% (122-192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104-153%) (P<0.05) on 200 mg/day and 240% (97-360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12. 7+/-2.6 (mean+/-SEM) to 16+/-3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4+/-2.0 to 19.2+/-3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA resembled that reported with another antioxidant, probucol. Some evidence has suggested that increased CETA is potentially deleterious and it might therefore counteract beneficial effects of vitamin E or probucol on the susceptibility of lipoproteins to oxidation.
Atherosclerosis 2000 May
PMID:Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity. 1078 43

Oxidative stress which results from an imbalance between reactive oxygen species production and antioxidant defense mechanisms is now well recognized in hemodialysis (HD) patients and could be involved in dialysis-related pathologies such as accelerated atherosclerosis, amyloidosis and anemia. In order to evaluate the rationale for preventive intervention against oxidative damage during HD, we review the factors that are implied and may be responsible for the imbalance between pro- and antioxidative mechanisms. The inflammatory state mainly due to hemobioincompatibility of the dialysis system plays a critical role in the production of free oxygen radical species contributing by this way to worsen the prooxidant status of uremic patients. Two factors largely contribute to the stimulation of the NADPH oxidase: hemoreactivity of the membrane and trace amounts of endotoxins. The antioxidant system is severely impaired in uremic patients and gradually altered with the degree of renal failure. HD could further impair this antioxidant system mainly by losses of (a) hydrophilic unbound small-molecular-weight substances such as vitamin C, (b) trace elements and (c) enzyme-regulatory compounds. Two main axes may be proposed in order to prevent and/or to decrease oxidative stress in HD patients. One consists in improving the hemocompatibility of the dialysis system mainly by using a dialyzer with low hemoreactivity and ultrapure, sterile, nonpyrogenic dialysate. The other consists in supplementing the deficiency patients with antioxidants. This could be achieved by oral or perdialytic supplementation. Vitamin E could be bound on dialyzer membrane. Alternatively, hemolipodialysis consists in loading HD patients with vitamin C or E via an ancillary circuit made of vitamin E-rich liposomes. The presence of liposomes could also facilitate the removal of hydrophobic prooxidative substances.
 ...
PMID:Why hemodialysis patients are in a prooxidant state? What could be done to correct the pro/antioxidant imbalance. 1085 22

The increased risk of atherosclerosis in nephrotic syndrome is attributable in part to the associated hyperlipidaemia. The importance of oxidation of LDL in the atherogenic process has been recognized over the last 15 years. However, there are few data on the balance of antioxidant defences and lipoprotein oxidation in nephrotic syndrome. Plasma antioxidant vitamin concentrations and indices of LDL oxidation (LDL lipid hydroperoxide content and the susceptibility of LDL to oxidation) were measured in two groups of patients; group I comprised 29 nephrotic patients and group II comprised 25 patients with haematuria. Plasma ascorbate concentration was significantly lower in group I (the nephrotic group) compared with group II (median 13.3 versus 22.2 micromol/L; P<0.001). Vitamin E concentrations were higher in group I but were not significantly different if corrected for total plasma cholesterol (6.12 versus 5.88 micromol/mmol; P=0.33). However, these changes resulted in a low ascorbate:vitamin E ratio in group I (0.19 versus 0.87; P<0.0001). Despite these changes in important antioxidant vitamin concentrations, we were unable to demonstrate any increased susceptibility to LDL oxidation in vitro or any difference in LDL lipid hydroperoxide content. These data suggest that there may be a relative defect of oxidant/antioxidant balance in nephrotic syndrome which could predispose to increased oxidative stress. However, measures of LDL oxidation were not significantly different between the two groups. LDL was protected from oxidation despite the severe hyperlipidaemia and the low circulating vitamin C concentrations.
 ...
PMID:Antioxidant vitamin concentrations and LDL oxidation in nephrotic syndrome. 1090 65

The development of atherosclerosis is a multifactorial process in which both elevated plasma cholesterol levels and proliferation of smooth muscle cells play a central role. Numerous studies have suggested the involvement of oxidative processes in the pathogenesis of atherosclerosis and especially of oxidised low density lipoproteins. Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of vitamin E and lower rates of ischemic heart disease. Recently, the Cambridge Heart Antioxidant Study (CHAOS) reported strong protection by high vitamin E doses against the risk of fatal and non fatal myocardial infarction. Here we have shown that incubation of vascular smooth muscle cells in the presence of alpha-tocopherol resulted in inhibition of cell proliferation and protein kinase C activity. Since beta-tocopherol and probucol are not inhibitory, the effect of alpha-tocopherol is considered due to a non-oxidant mechanism. In order to understand the protective role of alpha-tocopherol against atherosclerosis in vivo the following rabbit studies were carried out. Atherosclerosis was induced by a vitamin E poor diet containing 2% cholesterol in a group of rabbit. The other groups had 2% cholesterol in the diet plus 50 mg/kg vitamin E i.m. or 1% probucol or 50 mg/kg vitamin E plus 1% probucol. After 4 weeks, aortas were removed and analysed by microscopy for atherosclerotic lesions. Samples of the media were analysed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol induced atherosclerotic lesions and the induction of protein kinase C activity while probucol was not effective. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as probucol and, therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells in vitro and ex-vivo suggests an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.
 ...
PMID:Effect of vitamin E on the development of atherosclerosis. 1096 37

Several studies in macrophage cell lines, rodent macrophages, and animal models of atherosclerosis suggest that vitamin E may prevent the formation of foam cells. We tested this hypothesis in a recently developed, fully autologous in vitro model of human foam cell formation. During maturation, macrophages continuously increased their alpha-tocopherol/total cholesterol ratio, demonstrating that these cells accumulate alpha-tocopherol at an even higher rate than cholesterol. In the presence of unsupplemented serum, we observed no correlation between serum vitamin E levels and the increase in the cellular alpha-tocopherol/total cholesterol ratio. In contrast, under supplemented conditions, a 3.1-fold increase in the mean serum alpha-tocopherol/total cholesterol ratio resulted in a corresponding mean 3.5-fold increase in the cellular alpha-tocopherol/total cholesterol ratio. Vitamin E loading had no effect on the lipid composition of macrophages and did not affect their growth. Foam cell formation was stimulated in mature unsupplemented and vitamin E-loaded macrophages for 1 week with 50 microg autologous aggregated low density lipoprotein (LDL) in the presence of unsupplemented and vitamin E-loaded serum, respectively. We observed no effect of vitamin E supplementation on the formation of foam cells. However, foam cell formation resulted in a 36% and 44% reduction in the cellular alpha-tocopherol/total cholesterol ratio in unsupplemented and vitamin E-supplemented foam cells, respectively. The loss of vitamin E was accelerated with increasing concentrations of aggregated LDL and was accompanied by an increase in the susceptibility of these foam cells to succumb to the cell lytic effects of oxidized LDL (OxLDL). However, vitamin E supplementation did not protect macrophages or foam cells from OxLDL-mediated cell lysis, suggesting that vitamin E loss in foam cells is not the cause of their increased susceptibility to cell lysis. Our results suggest that the beneficial effects of vitamin E on cardiovascular disease observed in humans are due neither to a reduction in the propensity of macrophages to form foam cells nor to an increased resistance of these cells to cytolytic OxLDL.
 ...
PMID:Vitamin E supplementation of human macrophages prevents neither foam cell formation nor increased susceptibility of foam cells to lysis by oxidized LDL. 1097 52

We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not.
 ...
PMID:Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men. 1097 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>