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)

Data from several national surveys consistently show that American children have lower than recommended intakes of vitamin E, which is reflected in lower than average serum levels. Reduction in dietary fat can further exacerbate the low vitamin E status of children. The consequences of low vitamin E intake may include impaired immune responses, as seen in a study of over 500 Canadian children. Low vitamin E status has been correlated with increased risk of atherosclerosis and cardiovascular disease, cancer, cataract and impaired immune responses in adult populations. Since early signs of chronic degenerative diseases of aging have been seen in autopsies of children, efforts should be made to ensure that prolonged low intakes of vitamin E are avoided in children as well as adults.
 ...
PMID:Vitamin E status of US children. 150 6

Oxidized LDL, which has been discovered in vivo in areas of proximity to the atherosclerotic lesion, has been shown to enhance macrophage cholesterol accumulation. We studied the anti-oxidant potential of pravastatin, bezafibrate and cholestyramine in 18 patients with hypercholesterolemia. In addition, we examined the electrophoretic mobility and the uptake of LDL by macrophages before and after drug therapy. Pravastatin lowered plasma levels of LDL cholesterol by 57%, cholestyramine by 27% and bezafibrate by 25%. Pravastatin and bezafibrate also altered the composition of LDL as evidenced by the reduction of its cholesterol/apo B100 ratio. Pravastatin and bezafibrate reduced plasma triglyceride levels by 45% and 25%, respectively, whereas cholestyramine raised plasma triglyceride concentrations by 28%. LDL propensity for in vitro oxidation was analyzed following lipoprotein incubation with 10 microM copper ions and determination of LDL malondialdehyde (MDA), peroxides (PD) and conjugated dienes (CD) content. All drugs inhibited the susceptibility to in vitro oxidation of LDL isolated after drug therapy in comparison to LDL isolated before commencing drug therapy. Pravastatin reduced MDA content by 22%, PD by 18% and CD by 20%. Cholestyramine reduced LDL content of MDA by 41%, PD by 25% and CD by 63%. Bezafibrate reduced MDA by 41%, PD by 38% and CD by 45%. LDL vitamin E content was reduced after treatment with bezafibrate, pravastatin and cholestyramine by 49%, 36% and 8%, respectively. The electrophoretic mobility of LDL after all drug therapies was reduced in comparison to LDL obtained before therapy. Macrophage uptake of LDL assessed by either the cellular cholesterol esterification rate or by lipoprotein degradation was not affected by drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1992 Mar
PMID:Hypolipidemic drugs reduce lipoprotein susceptibility to undergo lipid peroxidation: in vitro and ex vivo studies. 159 93

Modified Watanabe heritable hyperlipidemic rabbits (M-WHHL) were fed either standard rabbit diet or diet supplemented with 0.5% wt/wt of the lipophilic antioxidant vitamin E (d,l-alpha-tocopherol). Animals of 10-12 weeks of age were divided into two groups matched for distribution of serum cholesterol levels at the beginning of the 12 week study period. A significant hypocholesterolemic response to vitamin E feeding was observed throughout the study. Vitamin E supplementation increased serum vitamin E levels approximately fourfold and restricted ex-vivo copper mediated oxidative modification of low density lipoprotein (LDL) as quantitated by fluorescence at 430 nm. Post mortem examination of aortic tissue revealed a significant (32%) inhibition of surface area lesion involvement in the arch region as determined by image analysis. It is concluded that administration of vitamin E to M-WHHL rabbits brings about a significant hypocholesterolemic response, confers on LDL significant protection against oxidative modification and either or both contribute to the inhibition of early aortic lesion development.
Atherosclerosis 1992 Jun
PMID:Dietary vitamin E and the attenuation of early lesion development in modified Watanabe rabbits. 163 69

Lipid peroxidation and the antioxidant status were studied in male patients having stable angina (SA) and unstable angina (UA) pectoris and the results were compared with that of controls. Lipid peroxides (LPx) and conjugated dienes (CD) were found to be elevated in patients with both SA (LPx: 3.96 +/- 1.07, P less than 0.001; CD: 357.09 +/- 66.23, P less than 0.01) and UA (LPx: 4.66 +/- 1.33, CD: 373.33 +/- 49.82, P less than 0.001) than in controls (LPx: 3.22 +/- 0.86, CD: 335.15 +/- 60.27). In SA, the erythrocytes expressed a diminished activity of superoxide dismutase (SOD) (SA: 435.59 +/- 76.02, control: 651.69 +/- 145.90, P less than 0.001) and normal activities of catalase and glutathione peroxidase, whereas in UA it showed enhanced activities of both SOD (UA: 735.72 +/- 145.67, P less than 0.01) and catalase (UA: 21.94 +/- 6.26, control: 18.69 +/- 6.37, P less than 0.01). A significant increase was also noticed in the levels of ceruloplasmin and vitamin E during both types of angina, but not alteration was observed in the levels of transferrin. Further, the patients with diabetes showed maximum levels of lipid peroxides compared to smokers and hypertensives. The level of lipid peroxides was also observed to increase with the severity of disease. This study indicates that free radicals are involved in the pathogenesis and progression of atherosclerotic heart disease.
Atherosclerosis 1992 Jun
PMID:Antioxidant status in relation to free radical production during stable and unstable anginal syndromes. 163 72

Reduced prostacyclin (PGI2) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI2 and other prostaglandins (prostaglandin E2 [PGE2], thromboxane A2 [TXA2], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI2 and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca2+ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI2, PGE2, and TXA2, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for D-alpha-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI2, PGE2, or TXA2 production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI2 production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus.
 ...
PMID:Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose. 164 Aug 48

Male mongrel rabbits, divided into 5 groups (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + selenium, (4) HFD + vitamin E, (5) HFD + selenium + vitamin E, were treated for 12 weeks. In the groups receiving selenium and/or vitamin E, the elevation of serum total lipids, beta-lipoproteins, total cholesterol and triglyceride was markedly suppressed. HDL cholesterol in these groups of animals was increased. The cytochrome P-450 content in liver microsomes was increased, and the concentration of malondialdehyde in the blood plasma of rabbits was significantly decreased, while thyroid hormones (T4, T3), cortisol and insulin level were increased. Surface area of the lipid deposits at 12 weeks measured planimetrically averaged 76% in HFD-fed animals but only 28% in selenium + vitamin E treated rabbits. The important finding of this study is that combination of selenium and vitamin E, results in an intensified effect on the improvement of metabolic processes and on the reduction of atherosclerotic plaque formation.
Atherosclerosis 1991 Mar
PMID:Effect of selenium and vitamin E on the development of experimental atherosclerosis in rabbits. 167 Feb 89

The effect of fish oil ingestion (10 g MaxEPA/day) on the susceptibility of plasma lipoproteins to peroxidation was examined in 20 smokers (study A and B) and 22 nonsmokers (study C). The subjects were examined at the onset of each study (baseline values), divided into control and experimental groups and reexamined 4 weeks later. Smokers were examined 40 h after abstention from smoking (0 time) and 90 min after acute smoking (4-6 cigarettes). The parameters studied were TBARS, which provide an indication of peroxidative injury, and metabolism of conditioned LDL by macrophages as a biological indicator. These parameters were significantly higher (P less than 0.05-0.001) when the 90 min values of smokers were compared to time 0. After 4 weeks of fish oil ingestion, a significant rise above baseline values (33-50%) in plasma and LDL TBARS was found in smokers examined at time 0 and after acute smoking. Peroxidative modification of LDL isolated from smokers fed fish oil resulted in significantly higher TBARS (34-41%) and its metabolism by macrophages was higher (65-139%) compared to baseline values. In nonsmokers, the baseline values of the above parameters were lower than in smokers. Ingestion of fish oil resulted in a significant rise in TBARS in plasma (33%), LDL (137%), conditioned LDL (36-40%) and metabolism of conditioned LDL (70%) by macrophages. In 6 nonsmokers and 4 smokers, 400 mg of vitamin E/day were given with the fish oil. In the nonsmokers, vitamin E counteracted the effect of fish oil more effectively than in the smokers. In the light of the present results, indiscriminate recommendation of fish oil supplementation to the population at large should be cautioned.
Atherosclerosis 1991 Oct
PMID:Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins. 175 84

Alpha-Tocopherol (vitamin E) protects against free radical damage, which has been implicated in aging, cancer initiation, and atherosclerosis. We have found that physiological concentrations of alpha-tocopherol specifically inhibited aorta smooth muscle cell (VSMC, line A7r5) proliferation and protein kinase C (PKC) activity. Other water and lipid soluble antioxidants were inactive. alpha-Tocopherol inhibition of PKC and of VSMC proliferation may represent a physiological mechanism, relevant to the onset of diseased states such as atherosclerosis.
 ...
PMID:Alpha-tocopherol (vitamin E) regulates vascular smooth muscle cell proliferation and protein kinase C activity. 189 54

Spontaneous atherosclerosis is largely an occlusive disease of medium-size arteries whose progression in a hyperlipidemic environment reflects chronic interactions among injury stimuli to the vessel wall and "responses to injury" by vascular tissue and certain blood components. Development of vessel lesions in animal models of spontaneous atherosclerosis and (at least in principle) in man largely reflects responses of three major cell types (vascular endothelial cells, vascular smooth muscle cells, monocytes-macrophages) as well as the content and distribution of lipids among various lipoprotein subclasses and the increased atherogenicity of modified (e.g., oxidized) lipoproteins. The severe clinical complications associated with spontaneous atherosclerosis, along with its rather common incidence in man, have focused attention on the prevention and therapy of this vascular disease state. Some pharmacological studies in animal models of spontaneous atherosclerosis and some retrospective epidemiological studies in man suggest that vitamin E, the principal (if not sole) lipid-soluble chain-breaking tissue antioxidant, might have therapeutic benefit as an antiatherosclerotic agent. This suggestion gains support from a variety of compelling in vitro evidence demonstrating direct influences of vitamin E on cells and lipoproteins likely involved in the pathogenesis of spontaneous atherosclerosis. Biochemical and cellular data indicate that the potential antiatherogenic activity of vitamin E could reflect its activities as a regulator of endothelial, smooth muscle, or monocyte-macrophage function, an inhibitor of endothelial membrane lipid peroxidation, a modulator of plasma lipid levels and lipid distribution among circulating lipoproteins, and a preventor of lipoprotein oxidative modification. On the other hand, there is a comparative lack of conclusive evidence from animal models regarding: (a) the importance to atherogenesis of vascular and cellular processes modulated by vitamin E; (b) the influence of vitamin E on these processes in vivo and, consequently, on the initiation/progression of spontaneous atherosclerosis. Therefore, pharmacologic investigation of vitamin E (and synthetic, vitamin E-like antioxidants) in nutritional and hyperlipidemic animal models of spontaneous atherosclerosis is required to establish whether any atherosclerotic impact is associated with vitamin E and, if so, what the mechanistic basis of the therapeutic benefit is. Such a line of experimental inquiry should also increase our understanding of the pathogenesis of atherosclerotic vessel disease per se.
 ...
PMID:Therapeutic potential of vitamin E in the pathogenesis of spontaneous atherosclerosis. 193 26

Rabbits fed a 1% cholesterol diet with or without the antioxidant butylated hydroxytoluene (BHT) developed typical atherosclerotic lesions. The addition of BHT gave higher levels of total cholesterol (+40%), triglycerides (+250%), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) in plasma. Despite the lower plasma lipid levels, the degree of atherosclerosis of the aortic surface was considerably higher in rabbits fed cholesterol than in the group treated with cholesterol and BHT. The mean atherosclerotic involvement was 18.6 +/- 4.4% in the former group and 5.9 +/- 1.7% in the latter group (p = 0.02). In all animals, there was a high correlation between the area of the arterial lesion and cholesterol content (r = 0.96). Serum levels of cholesterol autooxidation products (7-ketocholesterol and cholesterol 5 alpha,6 alpha-epoxide) were lower in the group of rabbits treated with BHT (p less than 0.005). Serum levels of vitamin E were slightly higher in the BHT group. There was no significant difference in the clearance of beta-VLDL between the two treatment groups after using either beta-VLDL from cholesterol-fed animals or beta-VLDL from BHT-fed animals. The results are in accord with the contention that oxidative modification of lipoproteins is important for the development of atherosclerosis and that antioxidants may have a protective effect. At present, however, other explanations cannot be completely excluded, for example, effects of antioxidants on immunologic factors or monocyte adhesion.
 ...
PMID:The antioxidant butylated hydroxytoluene protects against atherosclerosis. 198 93


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