Pro-resolving lipid mediators are leads for resolution physiology

Serhan, Charles N.

doi:10.1038/nature13479

Cited by 2,428 publications

(3,030 citation statements)

References 120 publications

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“…EPA and DHA are also converted to specialized proresolving lipid mediators, with EPA and DHA being the respective precursors of the E‐series and D‐series resolvins 32. The resolvins have been shown to stimulate the resolution of acute inflammation by stopping further neutrophil recruitment to inflamed tissues and stimulating nonphlogistic infiltration of monocytes, which differentiate into resolution macrophages 33. These resolution macrophages then phagocytize and clear apoptotic neutrophils and debris, a process termed efferocytosis, which is a key step in resolution and prevention of chronic inflammation 33, 34.…”

Section: Discussionmentioning

confidence: 99%

“…The resolvins have been shown to stimulate the resolution of acute inflammation by stopping further neutrophil recruitment to inflamed tissues and stimulating nonphlogistic infiltration of monocytes, which differentiate into resolution macrophages 33. These resolution macrophages then phagocytize and clear apoptotic neutrophils and debris, a process termed efferocytosis, which is a key step in resolution and prevention of chronic inflammation 33, 34. Recent research has shown that omega‐3 fatty acids may hasten the resolution of inflammation when converted to resolvins 32, 33.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

Alfaddagh

Elajami

Ashfaque

et al. 2017

JAHA

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BackgroundAlthough statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume.Methods and ResultsA total of 285 subjects with stable coronary artery disease on statins were randomized to omega‐3 ethyl‐ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega‐3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low‐density lipoprotein cholesterol ≤80 mg/dL. In the intention‐to‐treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups (P=0.14) but approached significance in the per protocol analysis (P=0.07). When stratified by age in the intention‐to‐treat analysis, younger omega‐3 subjects had significantly less progression of the primary endpoint, noncalcified plaque (P=0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega‐3 ethyl‐ester group (median % change [interquartile range], 5.0% [−5.7, 20.0] versus −0.1% [−12.3, 14.5], respectively; P=0.018). Among those on low‐intensity statins, omega‐3 ethyl‐ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [−12.8, 9.0] versus 4.8% [−5.1, 19.0], respectively; P=0.032). In contrast, those on high‐intensity statins had no difference in plaque change in either treatment arm.ConclusionsHigh‐dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well‐controlled low‐density lipoprotein cholesterol levels. The benefit on low‐intensity statin, but not high‐intensity statin, suggests that statin intensity affects plaque volume.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

Alfaddagh

Elajami

Ashfaque

et al. 2017

JAHA

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“…Efficient resolution of inflammation is an active process required to clear pathogens, avoid tissue damage, and restore function. 1,2 Unabated inflammation is an underlying cause of many chronic diseases. 3 Self-resolving inflammation is divided into an early-onset phase and a resolution phase.…”

Section: Inflammation and Its Natural Resolution Are Host-protectivementioning

confidence: 99%

The Protectin PCTR1 Is Produced by Human M2 Macrophages and Enhances Resolution of Infectious Inflammation

Ramon

Dalli

Sanger

et al. 2016

The American Journal of Pathology

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115

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Inflammation and its natural resolution are host-protective responses triggered by infection or injury. The resolution phase of inflammation is regulated by enzymatically produced specialized pro-resolving mediators. We recently identified a new class of peptide-conjugated specialized pro-resolving mediators that carry potent tissue regenerative actions that belong to the protectin family and are coined protectin conjugates in tissue regeneration (PCTR). Herein, with the use of microbial-induced peritonitis in mice and liquid chromatography-tandem mass spectrometryebased lipid mediator metabololipidomics, we found that PCTR1 is temporally regulated during self-resolving infection. When administered at peak of inflammation, PCTR1 enhanced macrophage recruitment and phagocytosis of Escherichia coli, decreased polymorphonuclear leukocyte infiltration, and counter-regulated inflammation-initiating lipid mediators, including prostaglandins. In addition, biologically produced PCTR1 promoted human monocyte and macrophage migration in a dose-dependent manner (0.001 to 10.0 nmol/L). We prepared PCTR1 via organic synthesis and confirmed that synthetic PCTR1 increased macrophage and monocyte migration, enhanced macrophage efferocytosis, and accelerated tissue regeneration in planaria. With human macrophage subsets, PCTR1 levels were significantly higher in M2 macrophages than in M1 phenotype, along with members of the resolvin conjugates in tissue regeneration and maresin conjugate families. In contrast, M1 macrophages gave higher levels of cysteinyl leukotrienes. Together, these results demonstrate that PCTR1 is a potent monocyte/macrophage agonist, regulating key anti-inflammatory and pro-resolving processes during bacterial infection. (Am J Pathol 2016, 186: 962e973; http://dx

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“…In stress, protein synthesis is increased but less than protein degradation. The substrates we are administrating may be harmful at the onset of ischemia reperfusion, inhibiting autophagy [13], but could also be helpful in limiting the critical decrease of cell ATP [14], preventing programmed cell death or resolving inflammatory processes, for example, n-3 fatty acids producing lipoxin and resolvin [15]. While nutrition may never be the magic bullet to cure critical illness, improved understanding and its skilled use may improve cell metabolism, thus allowing the organism to better cope with injury.…”

mentioning

confidence: 99%