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

Reactive oxygen species produced by the cells present in the arterial wall may cause oxidative damage to cellular components altering endothelial cell (EC) function. Changes in the EC function appear to play a key role in the pathogenesis of atherosclerosis. Human aortic endothelial cells (HAEC) were employed to investigate the protective role of vitamin E upon exposure of endothelial cells to oxidative stress in vitro. HAEC assimilate d-alpha-tocopherol from the media in a dose-dependent manner. Exposure of HAEC to 16.5 mM of the free radical generator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 16 h decreased cell viability (assessed by trypan blue exclusion) from 90 to 28%. HAEC preincubated with vitamin E at 15, 30, and 60 microM prior to the AAPH exposure resulted in a dose-dependent increase in resistance to oxidative stress and increased cell viability by 37, 66, and 85%, respectively. An increase in prostacyclin (PGI2) production by HAEC in response to AAPH exposure was correlated positively with cell damage and negatively with vitamin E concentration. Interleukin (IL)-1 production also increased in parallel with cell damage induced by AAPH. Vitamin E treatment significantly reduced IL-1 production after AAPH exposure. This modulatory role of vitamin E on HAEC function following exposure to an oxidative stress may reflect its antioxidant protection against lipid peroxidation.
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PMID:Effect of vitamin E on human aortic endothelial cell responses to oxidative injury. 888 1

Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.
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PMID:Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE. 888 65

Recent studies suggest that vitamin E may be an important preventative factor in the development and progression of atherosclerosis. In order to more clearly define the role of vitamin E in atherosclerosis, we measured vitamin E, conjugated diens, and lipid flurochromes, as well as cholesterol, triglycerides and phospholipid in arterial and venous tissue of 83 patients. Serum cholesterol and triglyceride levels were significantly higher (P < 0.05) in patients with aortic occlusive (AIOD) and aneurysmal (AAA) disease than in control organ donors (OD). Tissue cholesterol concentrations were significantly elevated in AAA tissue when compared to OD and tissue from patients with peripheral occlusive disease (POD). Tissue from patients with AIOD contained greater concentrations of phospholipid (PL) than were measured in patients with POD and in OD. Vitamin E concentrations were highest in POD tissue and approximately 3.0, 2.0, and 1.6 fold greater than OD, AIOD and AAA tissue respectively. Diene conjugates and lipid flurochromes, measures of early and intermediate products of lipid peroxidation, were markedly elevated in all diseased arterial tissue compared to controls. There were no significant differences in tissue or serum lipid levels between saphenous vein (SVBG) and diseased vein grafts (DVG). However, conjugated diene concentrations were elevated in DVG compared to SVBG. Vitamin E levels were significantly elevated in diseased arterial and venous tissue (AIOD, AAA, POD, DVG) removed from patients with diabetes (P = 0.013) and hypertension (P = 0.049) compared to those without these risk factors. Diabetes was the only risk factor associated with significantly increased (P = 0.005) levels of vitamin E when only data from atherosclerotic arterial tissue (AAA, POD, AIOD) were analyzed. These preliminary data provide additional evidence of altered vitamin E metabolism and free radical processes in the tissues of patients with various manifestations of atherosclerosis.
Atherosclerosis 1996 Oct 25
PMID:Vitamin E levels in human atherosclerotic plaque: the influence of risk factors. 890 54

The demonstration of lipid loaded macrophages in atherosclerotic tissue has led to the development of in vitro systems to elucidate the mechanisms involved in lipid accumulation. Here we have characterised the changes which occur in human monocyte-derived macrophage (MDM) lipids during culture in either human serum (HS) or foetal calf serum (FCS). MDM cultured in HS were rapidly converted to lipid filled foam cells, as assessed using HPLC analysis and oil red-O staining and compared with the same cells grown in FCS. However, the lipids which accumulated were predominantly triglycerides with smaller amounts of unesterified cholesterol (UC) and only traces of cholesteryl esters (CE). alpha-Tocopherol (alpha-TocH) was present at higher levels in MDM cultured in HS compared to the same cells grown in FCS. MDM lipid accumulation was dependent on the triglyceride-rich lipoprotein (TGRL) fraction of human serum; accordingly, supplementation of FCS with human TGRL also induced MDM lipid accumulation. The relationships between cellular lipid accumulation and secretion of apolipoprotein E (apo E) and lipoprotein lipase (LPL) as well as expression of the low density lipoprotein receptor-related protein (LRP) were also examined. MDM lipid accumulation was associated with increased apo E secretion but did not alter extracellular LPL activity. The lipid accumulation which was induced by HS was potently inhibited (but not reserved) by the inflammatory cytokine interferon-gamma (IFN gamma), and this was associated with decreased apo E production, LPL secretion and expression of LRP. These studies reveal striking differences in the lipid composition of MDM cultured in either HS or FCS, and indicate that oil red-O staining is not necessarily associated with cholesteryl ester accumulation in human macrophages. Furthermore, the effect that serum-induced lipid accumulation has on the specific MDM functions studied should be appreciated when developing in vitro macrophage models.
Atherosclerosis 1997 Jan 03
PMID:Regulation of serum-induced lipid accumulation in human monocyte-derived macrophages by interferon-gamma. Correlations with apolipoprotein E production, lipoprotein lipase activity and LDL receptor-related protein expression. 905 Nov 97

An important event in the pathogenesis of atherosclerosis is believed to be the oxidative modification of low-density lipoprotein (LDL) initiated by a free radical-driven lipid peroxidation process. Vitamin E acts as a lipophilic chain-breaking antioxidant, while water-soluble chain-breaking antioxidants such as vitamin C or uric acid suppress the oxidation of LDL initiated by aqueous radicals. In this study, we established a new method of measuring the lag time of inhibited lipid peroxidation using the lipophilic azo radical initiator V-70:2-2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) and investigated in vitro the susceptibility of LDL to oxidation using this method when lipid- and water-soluble antioxidants were added. When the lipid-soluble antioxidant, vitamin E, was added to LDL, the lag time was extended whereas a higher dose of vitamin E led to a shortened lag time of V-70-induced lipid peroxidation in LDL. These results suggest that vitamin E radicals (tocopheroxyl radicals) act as prooxidants during the autoxidation of LDL. It was also shown that the shortened lag time induced by higher doses of vitamin E was restored when lipid- and water-soluble antioxidants were added simultaneously, which suggests that vitamin E radicals derived from vitamin E are subsequently reduced by vitamin C to regenerate vitamin E. Thus, the interaction between lipid- and water-soluble antioxidants provides an important function in maintaining LDL resistance to oxidation.
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PMID:Effects of antioxidants on the oxidative susceptibility of low-density lipoprotein. 932 62

Elevated fasting insulin concentrations and insulin resistance have been associated with non-insulin-dependent diabetes mellitus (NIDDM), obesity, atherosclerosis, and hypertension. Vitamin E supplementation in persons with and without NIDDM may be related to greater insulin sensitivity (SI). The cross-sectional associations of the intake of vitamins E and C with SI and insulin concentrations were evaluated among African American, Hispanic, and non-Hispanic white men and women with a wide spectrum of glucose tolerance included in the Insulin Resistance and Atherosclerosis Study (IRAS) (n = 1151). Insulin sensitivity was measured by minimal model analysis of a 12-sample, insulin-modified, frequently sampled intravenous glucose tolerance test. Nutrient intake (including vitamin supplement use) was assessed with a food-frequency questionnaire modified to include foods consumed by the three ethnic groups. Linear-regression models were used, including rank of SI and the log of fasting insulin as the outcome variables. Pearson correlation coefficients for vitamins E and C in relation to rank SI were r = 0.07 (P = 0.01) and r = 0.07 (P = 0.02), respectively. After adjustment for total energy and BMI these associations were no longer statistically significant and did not differ between ethnic groups. Results were similar when vitamins E and C were combined in categories of low and high antioxidant intake. Models replicated with log of fasting insulin as the outcome variable also did not produce significant associations with vitamins E or C. Thus, these cross-sectional analyses do not support the hypothesis of improved SI with increased intake of vitamins E and C.
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PMID:Insulin sensitivity and intake of vitamins E and C in African American, Hispanic, and non-Hispanic white men and women: the Insulin Resistance and Atherosclerosis Study (IRAS). 935 42

The hypothesis that tea or dietary lipid-soluble antioxidants reduce atherogenesis by lowering the oxidizability of low-density lipoprotein (LDL) was investigated. Five groups of 20 female New Zealand white rabbits were fed a restricted amount of a high-fat (30 en%) semipurified diet supplemented with cholesterol (0.15%, w/w) for 21 weeks. The vitamin E content of the control diet was 40 mg/kg diet. The animals received either green tea or black tea in their drinking water or vitamin E (200 mg/kg diet) or beta-carotene (20 mg/kg). The serum cholesterol concentrations (in the order of 18-23 mmol/l) were not significantly different between the groups. Vitamin E was substantially increased as compared to controls in vitamin E supplemented animals (3-fold within 8 weeks in plasma and LDL; P < 0.01) and weakly (1.2-fold) by green and black tea (P < 0.05). Green tea consumption tended to reduce aortic lesion formation by 31% (24 +/- 3.2% versus 35 +/- 5.7% for control animals P = 0.11), while black tea, vitamin E and beta-carotene had no effect. This was in contrast to the resistance of isolated LDL to oxidation induced at high copper concentration. Green and black tea induced a 13% and 15% (P < 0.05) prolongation of the lag phase, respectively, with a correspondingly lower oxidation rate, while vitamin E increased the lag phase by 63% (P < 0.01) with a concomitant diminution of the oxidation rate and beta-carotene had no effect. Regression analysis showed that there was no relationship between the extent of atherosclerosis and LDL oxidizability or plasma malondialdehyde as marker of in vivo lipid peroxidation. The results of the present study raise the question whether LDL oxidizability (at least when tested at high induction rate ex vivo) is a primary causal mechanism in atherosclerosis in the cholesterol-fed rabbit. The suitability of the cholesterol-fed rabbit with extreme hypercholesterolaemia as a model to study antiatherosclerotic properties of dietary antioxidants, such as the tested polyphenols, is discussed.
Atherosclerosis 1997 Nov
PMID:Effects of green tea, black tea and dietary lipophilic antioxidants on LDL oxidizability and atherosclerosis in hypercholesterolaemic rabbits. 939 71

Two major modifications of low density lipoprotein (LDL) that can lead to macrophage cholesterol accumulation and foam cell formation include its oxidation and aggregation. To find out whether these modifications can already occur in vivo in plasma and whether they are related to each other, the oxidation and aggregation states of plasma LDL were analyzed in the apolipoprotein E-deficient (E degree) transgenic mice during their aging (and the development of atherosclerosis), in comparison to plasma LDL from control mice. Plasma LDL from the E degree mice was already minimally oxidized at 1 month of age in comparison to control mice LDL, and it further oxidized with age in the E degree mice but not in the control mice. At 6 months of age, the contents of the E degree mice LDL-associated cholesteryl ester hydroperoxides, thiobarbituric acid reactive substances, and conjugated dienes were higher by two, three, and twofold, respectively, in comparison to LDL from the young, 1-month-old E degree mice. We also investigated the LDL aggregation state in E degree mice. In the young E degree mice, LDL oxidation was shown in comparison to control mice, but in both groups of young mice their LDL was not aggregated. In the E degree mice, however, the LDL aggregation state substantially increased with age, by as much as 125% at 6 months of age compared to the 1-month-old mice, whereas no significant aggregation could be detected in plasma LDL from control mice at the same age. To question the possible effect of LDL oxidation on its subsequent aggregation, LDL oxidation was induced by either copper ions, or by the free radical generator 2,2-azobis-2-amidinopropane hydrochloride, or by hypochlorite. All these oxidative systems led to LDL oxidation (to different degrees) and resulted in a similar, substantial LDL aggregation. These oxidation systems also enhanced the susceptibility of LDL to aggregation (induced by vortexing) by 23%, 28%, or 40%, respectively. To further analyze the relationships between the lipoprotein oxidation and its aggregation, LDL (0.1 mg of protein/mL) was incubated with 5 mumol/L CuSO4 at 37 degrees C in the absence or presence of the antioxidant, vitamin E (25 mumol/L). In the absence of vitamin E, a time-dependent increment in LDL oxidation was noted, which reached a plateau after 2 hours of incubation. LDL aggregation, however, only started at this time point and reached a plateau after only 5 hours of incubation. In the presence of vitamin E, both LDL oxidation and its aggregation were reduced at all time points studied. We extended the vitamin E study to the in vivo situation, and the effect of vitamin E supplementation to the E degree mice (50 mg.kg-1.d-1 for a 3-month period) on their plasma LDL oxidation and aggregation states was studied. Vitamin E supplementation to these mice resulted in a 35% reduction in the LDL oxidation state and in parallel, the LDL aggregation state was also reduced by 23%. These reductions in LDL oxidation and aggregation states were accompanied by a 33% reduction in the aortic lesion area, in comparison to nontreated E degree mice. We conclude that in E degree mice, LDL oxidation, which already took place in the plasma, can lead to the lipoprotein aggregation. These modified forms of LDL were shown to be taken up by macrophages at an enhanced rate, leading to foam cell formation. Thus, the use of an appropriate antioxidant can inhibit the formation of both atherogenic forms of LDL.
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PMID:Plasma LDL oxidation leads to its aggregation in the atherosclerotic apolipoprotein E-deficient mice. 940 86

The preventive effect of vitamin E and Probucol against atherosclerosis in rabbits were compared. Atherosclerosis was induced by a 2% cholesterol-containing vitamin E-poor diet (5-10 ppm). Six groups of five rabbits each were studied. Group I (control) was fed on a vitamin E-poor diet. The other groups had the following supplements: group II, 50 mg/kg vitamin E i.m.; group III, 2% cholesterol; group IV, 2% cholesterol plus 50 mg/kg vitamin E i.m., group V, 2% cholesterol plus 1% Probucol; group VI, 2% cholesterol + 1% Probucol plus 50 mg/kg vitamin E i.m. After 4 weeks, aortas were removed and analyzed by light and scanning electron microscopy for atherosclerotic lesions. Samples of the media were analyzed 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. Probucol was not effective in preventing either cholesterol-induced atherosclerotic lesions or the induction of protein kinase C activity. 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 ex vivo suggest an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.
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PMID:Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits. 943 96

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


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