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

Oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of coronary artery disease (CAD). Macrophages take up oxidized LDL via scavenger receptors, which is not regulated by cellular cholesterol contents, and oxidized LDL stimulates cholesterol esterification and this results in cellular cholesterol accumulation and foam cell formation. Several papers have reported a positive correlation between the severity of coronary atherosclerosis and the oxidative susceptibility of LDL. Small, dense LDL, LDL rich in polyunsaturated fatty acids (PUFA) or LDL poor in antioxidants (vitamin E, beta-carotene, CoQ10) should be more susceptible to lipid peroxidation and possibly more atherogenic. Therefore, to prevent CAD, it is important not only to reduce LDL cholesterol levels but also to suppress the oxidative modification of LDL.
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PMID:[Modified low-density lipoprotein]. 785 94

Dietary antioxidants such as vitamin E, vitamin C, beta carotene and flavonoids may retard atherosclerosis by preventing low density lipoprotein oxidation. Observational epidemiological studies, including ecological correlations, case control and prospective studies, indicate that high vitamin E levels may be associated with decreased cardiovascular disease. Beta carotene may be protective among smokers and the elderly. Few studies have been able to show that vitamin C has a protective effect. A handful of intervention studies have examined the effects of vitamin E and beta carotene with mixed results. While few side effects of antioxidant supplementation are known, the results of current, large-scale studies in primary intervention must be awaited before recommendations can be made. Increased intake of fruits and vegetables that are rich in antioxidants is recommended.
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PMID:[Antioxidants and cardiovascular disorders--epidemiologic aspects. Should high risk patients receive supplementation?]. 785 18

Vitamin E supplementation has been reported to protect low density lipoprotein (LDL) from copper-induced oxidation and macrophage-mediated oxidation. We investigated the effect of in vitro vitamin E enrichment of LDL on the accumulation of [3H]cholesteryl ester (CE)-LDL and stimulation of cholesteryl ester formation in J774 macrophages. Vitamin E supplementation prolonged lag time (2.9-fold) before the initiation of copper-induced LDL oxidation. LDL, preincubated with 5 microM copper or with macrophages in Ham's F10 medium, accumulated in macrophages much more than did native LDL. However, following vitamin E enrichment, LDL accumulation was significantly reduced following oxidative stress. Vitamin E-enriched LDL also reduced the stimulation of cholesteryl ester formation in macrophages. Moreover, vitamin E enrichment of macrophages reduced the ability of the cells to oxidize LDL. The present results indicate that vitamin E supplementation protects LDL against copper-induced and macrophage-mediated oxidation, inhibits oxidation-dependent accumulation of LDL in macrophages, and prevents stimulation of cholesteryl ester formation in macrophages. Additionally we have provided evidence that intra-cellular enrichment with vitamin E prevents oxidative modification of LDL by macrophages.
Atherosclerosis 1994 Sep 30
PMID:Effects of supplementing with vitamin E on the uptake of low density lipoprotein and the stimulation of cholesteryl ester formation in macrophages. 785 73

New Zealand White rabbits were made hypercholesterolemic by feeding a high cholesterol diet (10 g/kg diet) with or without added antioxidants. The antioxidants used were either probucol (10 g/kg) or vitamin E (10 g/kg) plus vitamin C (0.6 g/kg). Serum cholesterol concentrations were monitored as a function of time. At the end of 10 wk, serum and lipoprotein vitamin E concentrations, the extent of oxidation of lipoprotein fractions (thiobarbituric acid reacting substances), the susceptibility of lipoprotein to oxidation in vitro (conjugated diene formation) and the extent of atherosclerosis (aortic area stained by Sudan IV and plaque thickness) were measured. Rabbits fed diets supplemented with vitamins E and C had markedly higher serum vitamin E concentrations, marked vitamin E enrichment in all lipoprotein fractions, less oxidation in VLDL and LDL and enhanced resistance of LDL to further in vitro oxidation, but did not have significantly less aortic atherosclerosis. Rabbits given supplemental probucol likewise exhibited reduced oxidation of lipoproteins. However, aortic atherosclerosis in these animals was significantly lower, as were serum cholesterol concentrations. Inhibition of lipoprotein oxidation itself was not sufficient to reduce atherosclerosis in cholesterol-fed New Zealand White rabbits.
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PMID:Treatment of cholesterol-fed rabbits with dietary vitamins E and C inhibits lipoprotein oxidation but not development of atherosclerosis. 796 95

There is increasing evidence that oxidative modification of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Homozygous familial hypercholesterolaemia (HFH) is characterized by premature, severe atherosclerosis. Drugs available at present are ineffective in lowering the markedly elevated LDL levels in this condition; antioxidant therapy to protect the LDL against oxidation may be of benefit. Probucol, the only drug shown to induce xanthoma regression in HFH, is a potent antioxidant, but it also lowers high-density lipoprotein cholesterol (HDL-C) levels, causing some concern. Vitamin E is a naturally occurring antioxidant that does not affect HDL-C levels. We have therefore evaluated the effect of long-term high dose vitamin E on xanthoma regression in HFH. Ten subjects with HFH, mean age 17 years (range 4-34), received vitamin E (400-1000 mg/dl alpha-tocopherol acetate/day) for a period of 23 months (range 12-27). There was a 4.2-fold increase in the mean serum vitamin E level (mean (S.D.) 49.7 (19.9) to 177.9 (45.6) mumol/l; P < 0.005), but no change in serum lipid or lipoprotein concentrations. Although there was an increase in the in vitro resistance of LDL to oxidation as determined by the duration of the lag phase during copper-mediated oxidation (116 (8.34) vs. 141.5 (9.23) min; P < 0.005) there was no xanthoma regression; in fact they progressed in 4 subjects. Unlike probucol, high dose long-term vitamin E has no demonstrable effect on xanthoma regression in HFH.
Atherosclerosis 1994 Jun
PMID:Lack of effect of high dose vitamin E on xanthoma regression in homozygous familial hypercholesterolaemia. 798 Jun 95

The ability to discriminate between stereoisomers of alpha-tocopherol was studied in five patients with abetalipoproteinemia (ABL) because an impairment in secretion of apolipoprotein B-containing lipoproteins might impede the normally enhanced plasma transport of RRR-alpha-tocopherol. An oral dose containing 3.7 g of each 2R, 4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate) and 2RS,4'RS,8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6 all rac-alpha-tocopheryl acetate) was administered, then the labeled and unlabeled alpha-tocopherol contents of plasma and red blood cells from multiple blood samples obtained at selected times up to 72 h following the dose were quantitated. ABL plasma contained about 1%-10% of the d3-RRR-alpha-tocopherol concentrations of normal subjects given only 150 mg of each isotope. Three of the patients discriminated between forms of alpha-tocopherol with ratios of RRR-/allrac-alpha-tocopherol > or = 1.8, similar to normals. These data suggest that the hepatic tocopherol binding protein is present and functional in ABL patients. Although two of the patients did not discriminate between stereoisomers of alpha-tocopherol, it is likely that this resulted from nearly a complete block in very low density lipoprotein (VLDL) secretion. Thus, the ability of ABL patients to absorb and transport orally administered vitamin E is markedly impaired and variable among patients.
Atherosclerosis 1994 Jul
PMID:Discrimination between RRR- and all-racemic-alpha-tocopherols labeled with deuterium by patients with abetalipoproteinemia. 798 Jul 5

Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO4. However, vitamin E efficiency was lower (9.6 +/- 4.2 versus 30.2 +/- 7.6 min/nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5 +/- 16.5 versus 58 +/- 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu(2+)-oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other oxidatively modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers. 798 Nov 76

In animal studies antioxidants have demonstrated antiatherosclerotic actions, but hitherto not in human studies. Prospective epidemiological data suggest that high doses of vitamin E have beneficial effects on major coronary heart disease. Unresolved questions concerning the role of LDL oxidation and antioxidants in atherosclerosis are discussed. It remains to be shown if antioxidants can retard lesion progression in humans, and by what mechanisms they are acting.
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PMID:Antioxidants and atherosclerosis progression: unresolved questions. 798 57

We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a).
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PMID:Metabolic determinants of the course of coronary artery disease in men. 798 12

Based on the analogy in mechanisms and events between the pathogenesis of atherosclerosis and the inflammatory reaction, we investigated the impact of human polymorphonuclear leukocyte (PMN) degranulation and oxidative process on high-density-lipoprotein (HDL) structure. HDL were incubated (37 degrees C) with PMN at a physiological ratio (370 nmol cholesterol-HDL/ml with 2 x 10(6) PMN/ml) for 15, 30 and 60 min with or without stimulating agent. PMN activation was assessed by measurement of superoxide anion generation and elastase production, which both reached peak concentration at 15 min. HDL apolipoproteins (apo) analysed by immunoblotting after SDS/PAGE and electrofocusing evidenced the following modifications: (a) a slow hydrolysis of apo AII and apo Cs; (b) a rapid hydrolysis of apo E; (c) a change in apo AI isoform distribution with an increase in the most acidic isoform (AI-2) at the expense of a less acidic form (AI-1); (d) a shift of the major apo AII isoform into two more basic forms. In contrast, no quantifiable lipid modification nor lipid oxidation, assessed by thiobarbituric-acid-reactive substances (TBARS) were noted. Despite a lack of variation of TBARS, a decrease in HDL vitamin E content by 80% was observed. Since this decrease was prevented by addition of superoxide dismutase in the medium, we concluded the occurrence of an oxidative process affecting HDL. Experiments with proteolytic inhibitors showed that elastase caused the proteolytic cleavage of apolipoprotein E, AII and Cs. In contrast, apo AI modification might involve both oxidative and proteolytic processes.
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PMID:Structural changes of high-density-lipoprotein apolipoproteins following incubation with human polymorphonuclear cells. 802 7


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