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

The cytotoxic effect of native high density lipoprotein (n-HDL) and oxidised high density lipoprotein (ox-HDL) on macrophages was studied and compared with that of low density lipoprotein (LDL). Copper-mediated oxidation of HDL and LDL was conducted in vitro and assessed by the analysis of conjugated dienes (CD). The kinetics of CD production during lipoprotein oxidation showed that HDL, relative to LDL, exhibited a shorter lag phase (47.7 +/- 17.8 vs. 82.9 +/- 24.5 min), higher diene production (242.2 +/- 23.0 vs 210.4 +/- 14.9 nmol/mg lipid) and reached maximal diene concentration in less time (100.0 +/- 35.4 vs 136.4 +/- 27.9 min). The maximal rate of CD production was 5.38 +/- 1.30 nmol/mg lipid/min for HDL and 4.42 +/- 0.60 nmol/mg lipid/min for LDL. Vitamin E concentration was higher in HDL than in LDL (2.76 +/- 0.41 vs. 2.19 +/- 0.33 micrograms alpha-tocopherol equivalent/mg lipid). Ox-HDL and oxidised LDL (ox-LDL), under the same experimental conditions, were cytotoxic to macrophages in a dose-dependent manner. At the same protein, or total mass concentration, ox-HDL was less cytotoxic than ox-LDL. However, when both lipoproteins were compared at the same lipid or cholesterol concentrations, ox-HDL was equally or more cytotoxic than ox-LDL. In conclusion, HDL is more susceptible to in vitro oxidation than LDL and the resultant modification of HDL converts this lipoprotein into a cytotoxic particle.
Atherosclerosis 1996 Aug 23
PMID:In vitro oxidised HDL exerts a cytotoxic effect on macrophages. 883 25

The authors studied the effect of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs. Adult mongrel dogs weighing 7.4 +/- 1.0 kg were divided into control, hypercholesterolemic and vitamin E groups. The animals in the hypercholesterolemic group were fed a diet enriched with cholesterol (5% w/w) and coconut oil (10% w/w) for 40 days. The vitamin E group received the same diet plus 400 IU of vitamin E during the last 15 days of the experiment. Total serum cholesterol levels were evaluated at the beginning and at the end of the experiment using a commercial enzyme kit and a Beckman analyzer. The coronary flow was determined by electromagnetic flowmetry using a probe positioned in the left anterior descending coronary artery, near the ostium. A needle connected to a perfusion pump was introduced into the coronary artery for the administration of acetylcholine and sodium nitroprusside at a rate of 5 micrograms/kg per min. The aorta was cannulated for the measurement of arterial blood pressure via a pressure transducer coupled to a Siemens multi-channel recorder. The tissue cholesterol content and malonic dialdehyde (MDA) were also measured in isolated coronary vessel specimens. At the end of 40 days, the serum cholesterol levels had increased by 226% and 190% in the hypercholesterolemic and vitamin E groups, respectively. However, the difference in the levels of these two groups was not significant (P > 0.05). The aortic blood pressure and heart rate remained unchanged during acetylcholine administration. In contrast, systolic and diastolic pressure fell and the heart rate increased during the infusion of sodium nitroprusside. The tissue cholesterol content and MDA were significantly (P < 0.05) increased in coronary artery specimens from the hypercholesterolemic compared to control animals. Vitamin E was able to reduce these increases in cholesterol treated animals (P < 0.05). The percent change in coronary flow during acetylcholine administration was significantly lower in the hypercholesterolemic group when compared with control animals (P < 0.05) but was unaltered in the vitamin E group (P > 0.05). During sodium nitroprusside administration, the coronary flow increased in the vitamin E group (P < 0.05). The authors conclude that hypercholesterolemia reduces endothelium-dependent coronary flow and increases the tissue cholesterol content and MDA of coronary arteries. Vitamin E decreases the MDA and the tissue cholesterol content without significantly affecting the total serum cholesterol level. Vitamin E may thus restore coronary flow by reverting endothelial dysfunction.
Atherosclerosis 1996 Sep 27
PMID:Effects of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs. 887 33

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

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


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