Biomedical subjects

S Devaraj

Publications and source records attributed to S Devaraj.

44 records · Page 3Linked to original sources

PubMed1996

Oxidized low-density lipoprotein and atherosclerosis.

Atherosclerosis is the leading cause of morbidity and mortality in western society. The most important risk factors for atherosclerosis include smoking, hypertension, dyslipidemia, diabetes and a family history of premature atherosclerosis. Several studies indicate that an increased plasma low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Many data support a proatherogenic role for oxidized LDL, and its in vivo existence. The oxidative susceptibility of LDL is increased with established cardiovascular risk factors, such as diabetes, smoking and dyslipidemia. Supplementation with antioxidants such as ascorbate and alpha to copherol can decrease LDL oxidation as well as cardiovascular mortality and thus shows promise in the prevention of atherosclerosis

Antioxidants↗

PubMed1996

The role of oxidized low density lipoprotein in atherogenesis.

An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerotic disease. Although the precise mechanism(s) via which LDL promotes atherogenesis remains to be elucidated, the oxidative modification of LDL may be a crucial mechanism. Several lines of evidence support a role for oxidatively modified LDL in atherogenesis. LDL can be oxidatively modified in cell-free systems by transition metals and by all the major cells of the arterial wall. Oxidatively modified LDL (Ox-LDL) is taken up by macrophage scavenger receptors, promoting cholesterol ester accumulation and foam cell formation. It also promotes atherosclerosis by recruitment and retention of monocytes in the intima, by its cytotoxicity toward endothelial cells and by stimulating monocyte adhesion to the endothelium. Several lines of evidence support the in vivo existence of Ox-LDL. The LDL of patients with atherosclerosis are more prone to oxidation; antibodies against epitopes on Ox-LDL have been positively correlated with the progression of atherosclerosis. The oxidation of LDL has been shown to be reduced by antioxidants, and in animal models, these antioxidants decrease atherosclerotic lesion formation. Thus, much evidence supports a role for oxidized LDL in atherogenesis.

Antioxidants↗

PubMed1996

Low-density lipoprotein oxidation, antioxidants, and atherosclerosis: a clinical biochemistry perspective.

Cardiovascular disease is the leading cause of mortality in westernized populations. An increased concentration of plasma low-density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Several lines of evidence support a role for oxidatively modified LDL in atherosclerosis and for its in vivo existence. Antioxidants have been shown to decrease atherosclerotic lesion formation in animal models and decrease LDL oxidation; the evaluation of LDL oxidation in vivo is therefore very important. However, there is a paucity of methods for direct measurement of LDL oxidation. Of the direct methods currently available, the preferred ones seem to be the measurement of F2-isoprostanes, autoantibodies to epitopes on oxidized LDL, and the assessment of antioxidant status. Of the indirect measures, the most uniformly accepted procedure is examining the oxidative susceptibility of isolated LDL by monitoring conjugated diene formation.

Antioxidants↗

PubMed1996

Oxalate binding to rat kidney mitochondria: induction by oxidized glutathione.

Increased oxalate binding with negative correlation with reduced glutathione content was observed during lipid peroxidation in rat kidney mitochondria. In presence of oxidized glutathione (GSSG), peroxidized mitochondria lost 48% of protein-SH with concomitant 3-fold increase in oxalate binding activity while control mitochondria lost only 20% protein-SH with only 0.8 fold increase in oxalate binding activity. The GSSG-induced oxalate binding was apparently due to two-fold increased affinity of oxalate to the protein. Reduced glutathione (GSH) inhibited oxalate binding competitively with Ki, 1.4 x 10(-3) M. Urolithic rat kidney mitochondria showed 30-50% increase in oxalate binding activity along with depletion of GSH and protein-SH. These studies suggest that oxalate binding is regulated by thiol status of mitochondria.

Animals↗

PubMed1996

Effect of alpha-tocopherol on LDL oxidation and glycation: in vitro and in vivo studies.

Much data support a role for both low density lipoprotein (LDL) oxidation and glycation in atherogenesis. While alpha-tocopherol decreases the oxidative susceptibility of LDL, its role in decreasing LDL glycation is unclear. Hence we tested the effect of alpha-tocopherol both in vitro and in vivo on LDL oxidation and glycation. LDL was isolated after enrichment of plasma with alpha-tocopherol. This resulted in a 2-fold increase in alpha-tocopherol in LDL (AT-LDL). During a 6-day incubation of control LDL (C-LDL) and AT-LDL with 25 mM glucose, there were no significant differences in the degree of glycation on days 1, 3, and 6. Also, apoB advanced glycosylation end product levels were not significantly different between C-LDL and AT-LDL. There was a progressive increase in the susceptibility of LDL to oxidation with increasing LDL glycation as evidenced by reduced lag time of copper-catalyzed LDL oxidation. However, AT-LDL was more resistant to copper-catalyzed oxidation. Similar findings were observed when the LDLs were incubated with endothelial cells. The data from the alpha-tocopherol supplementation study confirmed our in vitro findings that alpha-tocopherol significantly decreases oxidative susceptibility of LDL, but does not affect its glycation. Therefore, while glycation increases LDL oxidative susceptibility, alpha-tocopherol decreases the oxidation of glycated LDL but not LDL glycation.

Arteriosclerosis↗

PubMed1995

Comparison of an immunoprecipitation method for direct measurement of LDL-cholesterol with beta-quantification (ultracentrifugation).

A direct LDL cholesterol assay was evaluated using immunoprecipitation (Sigma Diagnostics, St. Louis, MO) with beta-quantification obtained by ultracentrifugation. Excellent intra- and interassay coefficients of variation were obtained (< 4.5%). There was a good correlation (r = 0.88, P < .0001) between the two methods for low-density lipoprotein cholesterol (LDL-C) in 249 samples with triglyceride levels ranging from 13 mg/dL to 2,236 mg/dL and LDL cholesterol levels ranging from 28 mg/dL to 290 mg/dL. Similar correlations were seen for patients with triglyceride levels < 400 mg/dL (r = 0.89, n = 174) and > or = 400 mg/dL (r = 0.89, n = 75). However, using the Friedewald equation, there was a good correlation only in samples with triglyceride levels < 400 mg/dL. No significant differences were found between LDL-C quantitated by the direct LDL assay and beta quantification for patients with dysbetalipoproteinemia (Type III disorder). However, calculated LDL values using the Friedewald equation were found to be significantly higher when compared to beta-quantification in patients with the Type III disorder. There was a slight but significant decrease in LDL-C determined by direct LDL cholesterol assay for non-fasting versus fasting serum (4.7%) despite a strong correlation between these samples (r = 0.98, P < .0001). In addition, freezing samples for 30 days resulted in a significant decrease in levels (15.1%). Thus, this direct LDL cholesterol assay is recommended in place of beta-quantification in hypertriglyceridemic samples (TG > or = 400 mg/dL) and to monitor LDL cholesterol levels in patients with Type III dyslipidemia, because it is less time consuming, more cost-effective and can be adapted to the clinical laboratory.

Cholesterol, LDL↗

PubMed1995

Effect of aging on susceptibility of low-density lipoproteins to oxidation.

According to the Adult Treatment Panel of the National Cholesterol Education Program, age is a major risk factor for heart disease. To assess the relation between age and LDL oxidizability, we studied copper-mediated LDL oxidation in 13 healthy elderly subjects (> 59 years) and 13 sex-matched healthy young controls (< 30 years). Total and LDL-cholesterol concentrations were increased in elderly subjects. The time course of copper-mediated LDL oxidation showed no significant differences between the two groups as assessed by formation of conjugated dienes, lipid peroxides, and apolipoprotein B fluorescence. Kinetics of LDL oxidation as quantified by lag time, oxidation rate, and maximal oxidation were not significantly different between the elderly and young groups. Although the concentrations of 16:0, 18:0, 18:1, 18:3, and 20:4 and total polyunsaturated fatty acids were significantly higher in the elderly group, LDL fatty acid concentrations were similar in both groups. Lipid-standardized alpha-tocopherol, beta-carotene, and ascorbate concentrations were not significantly different between the two groups. The findings of the present study suggest that in the healthy elderly, LDL oxidation may not be a crucial mediator for atherogenesis.

Adult↗

PubMed1991

Induction of oxalate binding by lipid peroxidation in rat kidney mitochondria.

Enhanced oxalate binding (150-180% of control) was observed in kidney, liver, brain and heart, after subjecting them to lipid peroxidation in presence of iron. Kidney mitochondrial oxalate binding was stimulated by different promoters, and the order of stimulation was Fe2+ greater than t-BH greater than ascorbic acid greater than Fe3+ greater than H2O2. Oxalate binding was maximum when iron concentration was between 1-2 mM. The iron-induced oxalate binding was inhibited by reduced glutathione, beta-mercaptoethanol, alpha-tocopherol and hydroxyl ion scavengers, histidine and mannitol. Catalase inhibited both Fe(2+)-H2O2 induced oxalate binding and lipid peroxidation reactions, suggesting that the induced oxalate binding in mitochondria was mediated through the hydroxyl radical reaction mechanism.

Animals↗