Specialized pro-resolving mediators: do they circulate in plasma?

Murphy, Robert C.

doi:10.1194/jlr.c062356

Cited by 18 publications

(17 citation statements)

References 9 publications

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“…(66) also found that fish oil supplementation could increase plasma levels of RvE1 in healthy human volunteers. On the other hand, others have questioned the relevance of circulating RvEs in humans consuming fish oil supplements (55, 58, 62, 63, 69). The reason for these discrepancies between studies remains unclear, but may relate in part to analyte stability, sample handling, and methodological and analytical differences (65).…”

Section: Discussionmentioning

confidence: 99%

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

et al. 2016

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In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach. Plasma was obtained from human subjects before and after 7 d of supplementation with pure n-3 DPA, n-3 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5 (RvD5) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E (15-keto-PGE). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the e-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids and their marked modulation by dietary DPA intake reveals a unique and specific role of n-3 DPA in human physiology.-Markworth, J. F., Kaur, G., Miller, E. G., Larsen, A. E., Sinclair, A. J., Maddipati, K. R., Cameron-Smith, D. Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid.

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Section: Discussionmentioning

confidence: 99%

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

et al. 2016

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“…Moreover, high intake of omega-3s could also bias the utilization of EPA and DHA away from SPM and toward the formation of free radical-initiated auto-oxidation products 82 . While the evidence to date indicates that SPM and their intermediate precursors are indeed produced in humans in vivo and are demonstrable by LC-MS/MS 74–76, 79, 83, 84 , it is noteworthy that with inadequate approaches and methodology, some studies were unable to identify endogenous SPM in plasma 85 , which have specific stereochemistry and require the use of commercially available deuterium-labeled standards for their definitive identification in human tissues. These are important considerations for the development and implementation of new therapeutic approaches and also suggest that targeted delivery of specific SPM may be a better therapeutic approach.…”

Section: Increasing Pro-resolving Lipid Mediators With Nutritional Anmentioning

confidence: 99%

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Sansbury

Spite

2016

Circulation Research

171

103

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Acute inflammation is a host-protective response that is mounted in response to tissue injury and infection. Initiated and perpetuated by exogenous and endogenous mediators, acute inflammation must be resolved for tissue repair to proceed and for homeostasis to be restored. Resolution of inflammation is an actively regulated process governed by an array of mediators as diverse as those that initiate inflammation. Among these, resolvins have emerged as a genus of evolutionarily conserved pro-resolving mediators that act on specific cellular receptors to regulate leukocyte trafficking and blunt production of inflammatory mediators, while promoting clearance of dead cells and tissue repair. Given that chronic unresolved inflammation is emerging as a central causative factor in the development of cardiovascular diseases, an understanding of the endogenous processes that govern normal resolution of acute inflammation is critical for determining why sterile maladaptive cardiovascular inflammation perpetuates. Here, we provide an overview of the process of resolution with a focus on the enzymatic biosynthesis and receptor-dependent actions of resolvins and related pro-resolving mediators in immunity, thrombosis and vascular biology. We discuss how nutritional and current therapeutic approaches modulate resolution and propose that harnessing resolution concepts could potentially lead to the development of new approaches for treating chronic cardiovascular inflammation in a manner that is not host-disruptive.

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“…Dietary fish oil (460 mg EPA and 380 mg DHA as ethyl esters for four weeks) did not increase levels of these pro-resolving lipids in the circulation [115]. Cytochrome-dependent epoxy-metabolites and lipoxygenase-dependent monohydroxy-metabolites which are partly precursors of resolvins were nevertheless found increased in blood and were supposed to contribute to the protective effects of fish oil intake [114,115,116]. …”

Section: Molecules Involved In Resolution Of Inflammationmentioning

confidence: 99%

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

Buechler

Pohl

Aslanidis

2017

IJMS

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Inflammation is a complex response of the body to exogenous and endogenous insults. Chronic and systemic diseases are attributed to uncontrolled inflammation. Molecules involved in the initiation of inflammation are very well studied while pathways regulating its resolution are insufficiently investigated. Approaches to down-modulate mediators relevant for the onset and duration of inflammation are successful in some chronic diseases, while all of them have failed in sepsis patients. Inflammation and immune suppression characterize sepsis, indicating that anti-inflammatory strategies alone are inappropriate for its therapy. Heme oxygenase 1 is a sensitive marker for oxidative stress and is upregulated in inflammation. Carbon monoxide, which is produced by this enzyme, initiates multiple anti-inflammatory and pro-resolving activities with higher production of omega-3 fatty acid-derived lipid metabolites being one of its protective actions. Pro-resolving lipids named maresins, resolvins and protectins originate from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid while lipoxins are derived from arachidonic acid. These endogenously produced lipids do not simply limit inflammation but actively contribute to its resolution, and thus provide an opportunity to combat chronic inflammatory diseases and eventually sepsis.

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Specialized pro-resolving mediators: do they circulate in plasma?

Cited by 18 publications

References 9 publications

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

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