Beyond Cholesterol

Steinberg, Daniel; Parthasarathy, S.; Carew, Thomas E.; Khoo, John C.; Witztum, Joseph L.

doi:10.1056/nejm198904063201407

Cited by 3,302 publications

(259 citation statements)

References 87 publications

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“…Plasma lipoproteins are an important target for oxidative lipid damage [31,33]. However, no shifts in electrophoretic mobility of the different plasma lipoprotein species [33] were observed by agarose gel electrophoresis [19] after exposing plasma to OJ (tested up to 12 h) when compared with air-exposed controls.…”

Section: Attempts To Measure Lipid Peroxidationmentioning

confidence: 99%

Oxidative damage to plasma constituents by ozone

et al. 1992

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The reaction of ozone (0,) with human blood plasma was studied to help understand possibleevcnts that could occur in the respiratory trtit. Uric acid (quantitatively the most important scavenger) and ascorbic acid were oxidized quickly, protcin.SH groups were lost more slowly, and there was no loss or bilirubin or a-tocopherol. There was little formation of lipid hydroperoxides and no detectable formation of Chydroxynoncnal, hexanal or nonanal, or changes in lipoprotein clcrtrophoretic mobility. Uric acid in human upper airway secretions may play a significant role in removing inhaled 0,. Oxidative damage to lipids must not bc assumed to be the key mechanism of mrpiratory tract 0, toxicity.

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Section: Attempts To Measure Lipid Peroxidationmentioning

confidence: 99%

Oxidative damage to plasma constituents by ozone

et al. 1992

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“…Numerous factors have been reported to contribute to posttransplant hyperlipidemia, including: steroids [4]; cyclosporine [5, 6]; level of renal function [7, 8]; diabetes mellitus, and the presence and degree of proteinuria [9, 10, 11, 12]. Oxidative modification of low-density lipoprotein (LDL) is a key event in early atherogenesis, which contributes to cholesterol accumulation in the arterial wall and the development of atherosclerotic lesions [13, 14, 15, 16, 17, 18, 19]. Oxidized LDL possesses additional atherogenic properties, which include cytotoxicity and stimulation of thrombotic and inflammatory events [14, 18, 20, 21].…”

Section: Introductionmentioning

confidence: 99%

Serum Paraoxonase Activity Changes in Uremic and Kidney-Transplanted Patients

Paragh¹,

Asztalos²,

Serés³

et al. 1999

Nephron

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Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36±30.12 vs. control 188.05±58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5±35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7±54.8) and kidney-transplanted patients (144.5±32.7) when compared to controls (194.5±94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31.62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.

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“…The pathogenesis of cardiovascular disease in chronic renal failure is multifactorial, including risk factors [13, 14]. The elevated lipid peroxidation plays a role in the changes of the vessel walls [15]. …”

Section: Introductionmentioning

confidence: 99%

The Serum Paraoxonase Activity in Patients with Chronic Renal Failure and Hyperlipidemia

Paragh¹,

Serés²,

Balogh³

et al. 1998

Nephron

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Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A₁) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A₁ levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A₁ level decreases, we standardized the enzyme activity for HDL and Apo-A₁ concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 ± 69.5) as compared with hyperlipidemic patients (137.64 ± 81.0) and controls (194.45 ± 94.45). The standardized values for Apo-A₁ showed a similar tendency: paraoxonase/Apo-A₁ ratio in uremic patients 89.64 ± 47.8, in hyperlipidemic patients 128.12 ± 69.83, and in controls 161.40 ± 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

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Beyond Cholesterol

Cited by 3,302 publications

References 87 publications

Oxidative damage to plasma constituents by ozone

Oxidative damage to plasma constituents by ozone

Serum Paraoxonase Activity Changes in Uremic and Kidney-Transplanted Patients

The Serum Paraoxonase Activity in Patients with Chronic Renal Failure and Hyperlipidemia

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