Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL particles in the rat

Newman, John W.; Kaysen, George A.; Hammock, Bruce D.; Shearer, Gregory C.

doi:10.1194/jlr.m700146-jlr200

Cited by 41 publications

(37 citation statements)

References 45 publications

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“…In the VLDL fractions used for HAEC treatments, the LA-derived oxidized lipids 13-HODE and 9-HODE were elevated .10-fold, whereas LA increased ?3-fold during the 30 min lipolysis process. In a recent study, Goodfriend et al (58) observed a remarkable increase in nonesterified oxylipids in plasma from subjects who received heparin, suggesting that human TGRLs contain these oxidized lipids in vivo, as observed in rats (51). Therefore, it appears that significant amounts of oxidized lipids are released during TGRL lipolysis, and may be involved in eliciting responses in exposed endothelium.…”

Section: Discussionmentioning

confidence: 99%

Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation

Wang

Gill

Pedersen

et al. 2009

Journal of Lipid Research

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Triglyceride-rich lipoprotein (TGRL) lipolysis products provide a pro-inflammatory stimulus that can alter endothelial barrier function. To probe the mechanism of this lipolysis-induced event, we evaluated the pro-inflammatory potential of lipid classes derived from human postprandial TGRL by lipoprotein lipase (LpL). Incubation of TGRL with LpL for 30 min increased the saturated and unsaturated FFA content of the incubation solutions significantly. Furthermore, concentrations of the hydroxylated linoleates 9-hydroxy ocatadecadienoic acid (9-HODE) and 13-HODE were elevated by LpL lipolysis, more than other measured oxylipids. The FFA fractions elicited pro-inflammatory responses inducing TNFa and intracellular adhesion molecule expression and reactive oxygen species (ROS) production in human aortic endothelial cells (HAECs). The FFA-mediated increase in ROS was blocked by both the cytochrome P450 2C9 inhibitor sulfaphenazole and NADPH oxidase inhibitors. Compared with linoleate, 13-HODE was found to be a more potent inducer of ROS production in HAECs, an activity that was insensitive to both NADPH oxidase and cytochrome P450 inhibitors. Therefore, although the oxidative metabolism of FFA in endothelial cells can produce inflammatory responses, TGRL lipolysis can also release preformed mediators of oxidative stress (e.g., HODEs) that may influence endothelial cell function in vivo by stimulating intracellular ROS production.-Wang, L., R. Gill, T. L. Pedersen, L. J. Higgins, J. W. Newman, and J. C. Rutledge. Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation. J. Lipid Res. 2009. 50: 204-213.

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Section: Discussionmentioning

confidence: 99%

Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation

Wang

Gill

Pedersen

et al. 2009

Journal of Lipid Research

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181

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“…Kreil et al observed an increase in lipoprotein oxylipids after hemorrhagic shock in human patients [5]. Newman et al have shown that experimental nephrosis in rats markedly increased the oxylipid content of lipoproteins [6].…”

Section: Discussionmentioning

confidence: 99%

Heparin, lipoproteins, and oxygenated fatty acids in blood: A cautionary note

Goodfriend¹,

Pedersen²,

Grekin³

et al. 2007

Prostaglandins, Leukotrienes and Essential Fatty Acids

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We measured 16 nonesterified oxygenated fatty acid derivatives (oxylipids) in plasmas from 7 human subjects. Two arterial samples from each subject were analyzed, drawn approximately two hours apart. We observed a marked increase in levels of most oxylipids in the second sample, as high as 470 fold. Between the first and second sample, subjects received approximately 800-1,000 IU of heparin to prevent clotting in intravascular catheters. We postulate that heparin activated lipoprotein lipases, which, in turn, released oxylipids from triglycerides and phospholipids in plasma lipoproteins. Some of that lipolysis may have occurred during sample storage. Measurements of nonesterified lipids in human plasma may be distorted if heparin is administered to subjects before blood is drawn and if lipase inhibitors are omitted from stored samples.

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“…We, thus, hypothesize that an effect modifier could modify the relationship between cholesterol and mortality. In CKD, both hypoalbuminuria and proteinuria could separately contribute to impaired lipoprotein catabolism and increased oxidative stress (14,15). We also propose that the relationship between cholesterol and mortality differs by amount of proteinuria.…”

Section: Introductionmentioning

confidence: 99%

Association of Cholesterol Levels with Mortality and Cardiovascular Events among Patients with CKD and Different Amounts of Proteinuria

Chen

Hung

Tsai

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Malnutrition and/or inflammation may modify the risk relationship of total cholesterol with cardiovascular disease in CKD patients. However, it is unclear whether the relationship of total cholesterol with cardiovascular events and mortality varies by proteinuria. Results During a median 2.8-year follow-up, there were 471 (14.3%) deaths and 545 (16.5%) cardiovascular events. In an adjusted Cox model, the two highest quartiles of total cholesterol (hazard ratio, 1.90; 95% confidence interval, 1.16 to 3.13 and hazard ratio, 2.00; 95% confidence interval, 1.18 to 3.39 versus quartile 1, respectively) were associated with a significant higher risk of all-cause mortality in patients with urine protein-to-creatinine ratio,1 g/g (n=1535), but this higher risk was not seen in those patients with urine protein-to-creatinine ratio$1 g/g (n=1768; hazard ratio, 0.75; 95% confidence interval, 0.53 to 1.07 and hazard ratio, 0.70; 95% confidence interval, 0.49 to 1.02 versus quartile 1, respectively). The interaction between total cholesterol and proteinuria with all-cause mortality was significant (interaction, P=0.05). However, the relationship between total cholesterol and cardiovascular events did not significantly differ by proteinuria (interaction, P=0.91). ConclusionsThe association between cholesterol and mortality is different among patients with different levels of proteinuria. Large-scale clinical trials to evaluate the mortality benefit should specifically target lowering hypercholesterolemia in CKD patients with different levels of proteinuria.

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Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL particles in the rat

Cited by 41 publications

References 45 publications

Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation

Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation

Heparin, lipoproteins, and oxygenated fatty acids in blood: A cautionary note

Association of Cholesterol Levels with Mortality and Cardiovascular Events among Patients with CKD and Different Amounts of Proteinuria

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