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

Goodfriend, Theodore L.; Pedersen, Theresa L.; Grekin, Roger J.; Hammock, Bruce D.; Ball, Dennis L.; Vollmer, Alan

doi:10.1016/j.plefa.2007.10.012

Cited by 27 publications

(15 citation statements)

References 14 publications

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“…The observed concentration of hydroxy-, epoxy- and dihydroxy-FA in serum were well in line with previously described levels of these oxylipins in plasma [11]. The oxylipin concentration in plasma can be strongly effected by the anticoagulant used [45]. Serum is a standard matrix which is used for the analysis of many biochemical parameters in blood and can be obtained in highly reproducible quality.…”

Section: Discussionsupporting

confidence: 87%

Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men

Schmidt

Kressel

Dong

et al. 2013

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Oxylipins, the oxidation products of unsaturated fatty acids (FA), are potent endogenous mediators being involved in regulation of various biological processes such as inflammation, pain and blood coagulation. Compared to oxylipins derived from arachidonic acid (AA) by cyclooxygenase action, i.e. prostanoides, only limited information is available about the endogenous levels of hydroxy-, epoxy- and dihydroxy-FA of linoleic acid (LA), AA, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans. Particularly, it is unknown how metabolic disorders affect endogenous oxylipin levels in humans. Therefore, in the present study we compared the serum concentrations of 44 oxylipins in 20 normolipidemic with 20 hyperlipidemic (total cholesterol > 200 mg/dl; LDL-C > 130 mg/dl; TG > 150 mg/ml) men (age 29–51 y). The serum concentration varied strongly among subjects. For most hydroxy-, epoxy- and dihydroxy-FA the concentration were comparable to those of plasma reported in earlier studies. Despite the significant change in blood lipid levels the hyperlipidemic group showed only minor differences in oxylipin levels. The hyperlipidemic subjects had a slightly higher serum concentration of 8,9-DiHETrE, 5-HEPE, 10,11-DiHDPE, and a lower concentration of 12,13-DiHOME, 12-HETE, 9,10-DiHODE, and 12,13-DiHODE compared to normolipidemic subjects. Overall the hydroxy-, epoxy- and dihydroxy-FA levels were not changed suggesting that mild combined hyperlipidemia has no apparent effect on the concentration of circulating oxylipins. By contrast, serum levels of several hydroxy-, epoxy-, and dihydroxy-FA are dependent on the individual status of the parent FA. Particularly, a strong correlation between the EPA content in the erythrocyte membrane and the serum concentration of EPA derived oxylipins was observed. Given that the synthesis of EPA from other n3-FA in humans is low, this suggests that oxylipin levels can be directly influenced by the diet.

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Section: Discussionsupporting

confidence: 87%

Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men

Schmidt

Kressel

Dong

et al. 2013

Prostaglandins, Leukotrienes and Essential Fatty Acids

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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: 95%

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

Wang

Gill

Pedersen

et al. 2009

Journal of Lipid Research

250

181

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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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“…A particular issue related to the measure of oxylipins in blood is the potential effects of the blood collection process as well as serum/plasma generation upon the observed oxylipin profile . Accordingly, it is essential that blood collection, processing, and handling methods are reported in detail when providing oxylipin data.…”

Section: Discussionmentioning

confidence: 99%

Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega‐3 fatty acids

Lundström

Yang

Brannan

et al. 2013

Molecular Nutrition Food Res

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Scope In contrast to well-characterized polyunsaturated fatty acid (PUFA) levels in serum, little is known regarding their downstream metabolic products. However, many of these compounds are lipid mediators with prominent roles during pro- and anti-inflammatory processes. Methods and Results In this double blind crossover study on asthmatics, shifts in serum levels of ω-3 and ω-6 PUFA-derived oxidized fatty acids (e.g., eicosanoids, oxylipins) were quantified following dietary fish oil supplementation. Serum was obtained from subjects following fasting at 3 occasions; 1) Prior to supplementation, 2) Following a 3-week supplement intake of either placebo or fish oil, and 3) Following a 3-week washout period with a subsequent 3-week period of either fish oil or placebo supplement. A total of 87 oxylipins representing cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary alterations observed were in CYP- and 15-LOX-derived EPA- and CYP-derived DHA oxylipins. Conclusion The results indicate that intake of an ω-3 rich diet altars not only the PUFA ratio, but also the ratio of downstream oxylipins. These data further support that dietary manipulation with ω-3 PUFAs affects not only PUFA levels, but importantly also the downstream metabolic profile.

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

Cited by 27 publications

References 14 publications

Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men

Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men

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

Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega‐3 fatty acids

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