Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Antioxidant vitamin concentrations and LDL oxidation in nephrotic syndrome. 1090 65

The aim of this study was to investigate the effects of cholestyramine in combination with statins on vitamin E levels and their concentration related to LDL-cholesterol (LDL-C) in patients with hyperlipidemia. In an open-label, randomized study of 25 patients with elevated LDL-C, 12 received cholestyramine (12 g/d) in addition to chronic statin therapy, which had been started at least 8 weeks prior to the study in all patients. At the start and end of the 12-week study period, vitamin E concentrations were measured by high-performance liquid chromatography and cholesterol and triglycerides enzymatically in all patients. Vitamin E levels remained virtually unchanged within normal range before (11.90 +/- 0.71 mg/l) and after 12 weeks (11.69 +/- 0.82 mg/l) of concomitant therapy with cholestyramine. However, the ratio of vitamin E/LDL-C increased from 7.48 +/- 0.56 to 8.58 +/- 0.75 (x 10(-2)) (p < 0.09) in the cholestyramine group but not in the control group. LDL-C concentrations decreased from 162.00 +/- 5.98 to 144.33 +/- 12.48 mg/dl. The authors conclude that cholestyramine 12 g/d given for 12 weeks in addition to chronic statin therapy did not lower vitamin E levels in hyperlipemic patients. However, antioxidant status (vitamin E/LDL-C ratio) seems to be improved by a cholestyramine-associated LDL-C decrease.
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PMID:Effects of cholestyramine on vitamin E levels in patients treated with statins. 1118 69

Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary disease and also inhibits the proliferation of VSMCs in vitro. We used vitamin E and probucol to treat glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two animal models of glomerular disease. Using rats, a remnant kidney model accelerated with hyperlipidemia was employed to reflect progressive glomerular sclerosis leading to chronic renal failure, and an anti-thymocyte serum treatment was used to model acute MC-proliferative GN. Supplemental dietary antioxidants suppress MC proliferation and glomerular sclerosis in models of glomerular disease in rats. These results suggest that treatment with antioxidants may be a promising intervention to prevent progression of kidney disease.
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PMID:Effects of antioxidants on kidney disease. 1204 53

We investigated the pathophysiological significance in biomembranes of the redox dynamics of Vitamin E (alpha-tocopherol) which is lipophilic radical scavenger related to aging or pathologic status such as non-insulin-dependent diabetes mellitus or primary hyperlipidemia. Vitamin E eliminates lipid peroxyl radicals by the peroxidation chain reaction of the membrane lipid, and it becomes Vitamin E radical. Furthermore, the Vitamin E radical becomes Vitamin E quinone which is an oxidic metabolite of Vitamin E. Therefore, it was needed to determine the alpha-tocopherol and alpha-tocopherolquinone simultaneously to evaluate the antioxidative status of alpha-tocopherol in biomembranes exactly. For this purpose, we developed the assay method for the simultaneous determination of the two substances using HPLC system. Then we applied this method to basic and clinical research. 1) For the simultaneous determination of alpha-tocopherol and alpha-tocopherolquinone, highly-sensitive measurement system by HPLC-multiple coulometric ECD was developed. This system is useful to estimate the redox dynamics of alpha-tocopherol in biomembranes. 2) The utilization rate of alpha-tocopherol in the erythrocyte membrane of 10- to 120-week-old rats was significantly increased, whereas alpha-tocopherol uptake in the erythrocyte membrane decreased age-dependently. Furthermore, a significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of the erythrocyte membrane were seen with age. 3) There was a strongly significant positive correlation between age and the utilization rate of alpha-tocopherol in the erythrocyte membrane of healthy volunteers aged between 23 and 103. 4) The alpha-tocopherol uptake in erythrocyte membrane was significantly lower in elderly non-insulin-dependent diabetes mellitus patients (average 68.1 years old) than in healthy subjects (average 71.8 years old). 5) The utilization rate of alpha-tocopherol in erythrocyte membrane and the alpha-tocopherol uptake in erythrocyte membrane were significant lower in elderly patients with primary hyperlipidemia (average 74.1 years old) compared to healthy subjects (average 71.2 years old). These findings suggest that the redox dynamics of alpha-tocopherol in biomembranes should be investigated with special regard to the onset, aggravation and complications of several diseases or aging as a result of oxidative stress. In addition redox dynamics were suggested to be useful to evaluate the grade of aging.
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PMID:[Relationship between aging and vitamin E]. 1240 40

Vitamin E homeostasis in hyperlipidemia is poorly understood. The biokinetics of deuterated alpha-tocopherol (alpha-T) in blood components was investigated in normolipidemic (N; total cholesterol < 5.5 mmol/L and triglycerides < 1.5 mmol/L, n = 9), hypercholesterolemic (HC; total cholesterol > 6.5 mmol/L and triglycerides < 1.5 mmol/L, n = 10), and combined hypercholesterolemic and hypertriglyceridemic (HCT; total cholesterol > 6.5 mmol/L and triglycerides > 2.5 mmol/L, n = 6) subjects. Subjects ingested 150 mg hexadeuterated RRR-alpha-tocopheryl acetate, and blood was collected up to 48 h after ingestion. Labeled alpha-T was measured in plasma, lipoproteins, erythrocytes, platelets, and lymphocytes by liquid chromatography/mass spectroscopy. In plasma, HC had an earlier time of maximum concentration (6 h) compared with N and HCT (12 h) (P < 0.05). HCT had a lower uptake of labeled alpha-T (P < 0.005) and a longer half-life (P < 0.05). In chylomicrons, the maximum labeled alpha-T concentration was higher in HC compared with N and HCT (P < 0.00005); however, HCT had a lower uptake of labeled alpha-T in LDL. In all groups, the lowest density LDL subfraction contained more labeled alpha-T than denser subfractions (P < 0.05). In platelets, lymphocytes, and erythrocytes, the areas under the labeled alpha-T concentration vs. time curves were in the order N > HC > HCT. In lymphocytes, differences in labeled alpha-T were found at 6 and 48 h (P < 0.05). These data demonstrate that there are differences in the uptake of newly absorbed alpha-T into blood components in hyperlipidemia. Because these blood components are functionally affected by vitamin E, reduced uptake of alpha-T may be relevant to the pathogenesis of atherosclerosis.
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PMID:Hyperlipidemic subjects have reduced uptake of newly absorbed vitamin E into their plasma lipoproteins, erythrocytes, platelets, and lymphocytes, as studied by deuterium-labeled alpha-tocopherol biokinetics. 1562 33

The advent of statins has virtually resolved the treatment of a majority of essential hypercholesterolaemic patients. Nevertheless, other abnormalities in lipoprotein metabolism, including such lipoprotein disturbances as hypertriglyceridaemia, mixed hyperlipidaemia, accumulation of small dense low density lipoprotein (LDL), high levels of lipoprotein (a) (Lp[a]) and hypo-HDL-cholesterolaemia, although also highly atherogenic, are not as efficiently treated as essential hypercholesterolaemia. Pharmaceutical companies are improving new molecules directed against old targets (PPARalpha: fibrates) or creating original molecules directed against new targets (acyl CoA:cholesterol acyltransferase (ACAT), microsomal triglyceride transfer protein (MTP), retinoid X receptor (RXR)). Of the multitude of ACAT inhibitors, only a few have reached preliminary clinical studies: e.g., F-1394, Sch48461 and CI-1011. They reduce LDL-cholesterol and atherosclerosis development in animals, partly by directly inhibiting cholesteryl ester formation in the artery wall. BW-USC-148 is a fibric acid derivative with ACAT-inhibiting activity. The hypocholesterolaemic activity for this novel ureido fibrate analogue was found to be over 100-fold greater than that of any 'second generation' fibrate in cholesterol-fed rats, mainly through its fibrate activity (PPARalpha activation) but not its ACAT activity. Targretin (LGD1069), a member of the rexinoid family (RXR activator), was shown to decrease triglyceridaemia and to increase HDL levels in hypertriglyceridaemic rats. Microsomal triglyceride transfer protein inhibitors are potent inhibitors of the synthesis of all the atherogenic apolipoprotein B-containing particles and are under development, but in vivo data are not yet available in literature. Vitamin E, an old molecule, should be used in the near future as a potent anti-atherosclerotic treatment due to its anti-oxidant power. Results of preliminary gene therapy studies of homozygous familial hypercholesterolaemic patients and of hypo-HDL-cholesterolaemia in animals are promising but do not show hope for significant clinical use in the near future. The improvement in the understanding of the molecular mechanisms of dyslipoproteinaemia and atherosclerosis development, taken together with new strategies in drug design and drug synthesis, has led to the discovery of potent normolipidaemic drugs.
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PMID:Post-statin approaches to hyperlipidaemia. 1599 42

In type 2 diabetics, the progression of atherosclerosis is more rapid than the general population and 80% of these patients will die of an atherosclerotic event. Since in these patients hyperglycemia per se confers increased risk for cardiovascular disease (CVD), the presence of even borderline-high-risk LDL-C signals the need for more aggressive LDL-lowering therapy. Most of the lipid lowering agents, currently in use in the treatment of dyslipidemia in type 2 diabetics, have a host of side effects. In contrast, dietary tocotrienols are Vitamin E and have effective lipid lowering property in addition to their potent antioxidant activity. In this study, we have investigated the therapeutic impacts of tocotrienols on serum and lipoprotein lipid levels in type 2 diabetic patients. Based on known tocotrienol rich fraction (TRF)-mediated decrease on elevated blood glucose and glycated hemoglobin A(1C) (HbA(1C)) in diabetic rats, we have also investigated the effect of TRF on these parameters. A randomized, double blind, placebo-controlled design involving 19 type 2 diabetic subjects with hyperlipidemia was used. After 60 days of TRF treatment, subjects showed an average decline of 23, 30, and 42% in serum total lipids, TC, and LDL-C, respectively. The goal in type 2 diabetics is to reduce LDL-C levels < or = 100mg/dl. In the present investigation tocotrienols mediated a reduction of LDL-C from an average of 179 mg/dl to 104 mg/dl. However, hypoglycemic effect of TRF was not observed in these patients because they were glycemically stable and their glucose and HbA(1) levels were close to normal values. In conclusion, daily intake of dietary TRF by type 2 diabetics will be useful in the prevention and treatment of hyperlipidemia and atherogenesis.
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PMID:The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. 1615 10

Vitamin E is a natural antioxidant that has been used in animal and human studies to determine its potential in reducing cardiovascular risk; however, a detailed study in an established obese model of atherosclerosis has yet to be performed. In our current study, we show that obesity and hyperlipidemia cause a synergistic, age-related increase in urinary isoprostane levels in mice deficient in both leptin and low-density lipoprotein receptor (ob/ob;LDLR-/-). Based upon this observation, we hypothesized that vitamin E supplementation would induce potent antiatherogenic effects in this model. Lean and obese LDLR-/- mice were provided vitamin E (2000 IU/kg) in a Western-type high-fat diet for 12 weeks. Plasma lipid parameters, such as total cholesterol (TC), triglyceride (TG) and free fatty acid, were significantly higher in obese mice compared to lean mice at baseline (P<.001). Western-type diet (WD) feeding caused an increase in TC levels in all groups (P<.001); however, TG (P<.001) and free fatty acid (P<.01) were elevated only in lean mice following WD feeding. Vitamin E supplementation neither influenced any of these parameters nor reduced urinary isoprostanes in lean or obese mice. Vitamin E supplementation in ob/ob;LDLR-/- mice resulted in a trend toward a reduction in atherosclerotic lesion area (P=.10), although no differences in lesion area were noted in lean LDLR-/- animals. These data provide evidence that vitamin E supplementation is not sufficient to reduce extreme elevations in systemic oxidative stress due to hyperlipidemia and obesity and, thus, may not be cardioprotective in this setting.
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PMID:Effects of vitamin E on oxidative stress and atherosclerosis in an obese hyperlipidemic mouse model. 1678 57

Atorvastatin calcium (AC) is a second-generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor approved for clinical use as a lipid lowering agent. AC, the world's best selling drug is associated with poor oral bioavailability and serious adverse effects like rhabdomyolysis on chronic administration. A biodegradable nanoparticulate approach was introduced here with a view to improving the efficacy and safety of AC. Poly lactide-co-glycolic acid (PLGA) nanoparticles containing atorvastatin calcium were prepared using two stabilizers i.e. didodecyl dimethyl ammonium bromide (DMAB) and Vitamin E tocopheryl polyethylene glycol 1000 succinate (Vit E-TPGS) using a co-solvent approach by emulsion-diffusion-evaporation method. AC loaded PLGA nanoparticles prepared using DMAB and Vit E-TPGS were found to be 120.0 +/- 4.2 nm and 140.0 +/- 1.5 nm (z-average) in size respectively. In vitro release studies at pH 7.4 revealed a zero order release profile for nanoparticles. Efficacy and safety parameters of the prepared nanoparticles against marketed formulation were evaluated in high fat diet fed (hyperlipidemic) rats. It was found that atorvastatin calcium nanoparticles were equally effective in comparison to Lipicure, at a 66%-reduced dose in treating the hyperlipidemia characterized by alterations in PTC, LDL-C, VLDL-C, HDL-C, PTG and PGL in the high fat diet fed rats. On the other hand, when evaluated for safety, nanoparticulate formulation showed no/negligible myotoxicity characterized by lower PC, BUN, CK, LDH and AST levels in comparison to the marketed formulation.
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PMID:Oral nanoparticulate atorvastatin calcium is more efficient and safe in comparison to Lipicure in treating hyperlipidemia. 1819 8

During aging there is a tendency towards hyperlipidemia and changes in the distribution of lipoproteins. A decline in the functioning of the body's antioxidant defense system is also observed at this time. The objective of this study was to establish the relationship between serum concentrations of total cholesterol and fractions, triglycerides, and Vitamins C and E. 61 adults over 60 years of age were evaluated from January to March, 2006. Nutritional status was diagnosed by BMI (WHO); serum levels of triglycerides (TG), total cholesterol (TC) and fractions (HDL-c and LDL-c) were determined by enzyme method; Vitamin C (colorimetric method) and Vitamin E by HPLC. ATPIII values were used as a reference for risk of TG, TC, HDL, LDL-c, vitamin C: > 0.9 mg/dL (normal), < 0.9 mg/dL (deficit); vitamin E: = 1300 microg/dL (normal), 1300 = microg /dL (deficit). Consumption of vitamins C and E were estimated by the direct weighing method 3 days per week. According to BMI, 19.7% had nutritional deficit, 39.3% overweight, and 11.5% obesity. TG, TC, LDL-c levels were at risk in females, and HDL-c in both genders. Prevalence of risk for heart disease was: TG (45.2%), HDL-c (51.1%), and LDL-c (52.5%). Consumption and serum levels of vitamin E were low in both genders. There was no association between variables. A significant and positive correlation between TG, TC, LDL-C, serum vitamin E, and BMI was observed. The female group showed overweight, hypertriglyceridemia and hypercholesterolemia, HDL-c and LDL-c at risk, and vitamin E deficiency, all of which are important risk factors for cardiovascular disease in this age group.
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PMID:[Relationship between serum lipids and status of vitamin C and E as antioxidants in Venezuelan elderly people]. 1936 97


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