An eicosanoid-centric view of atherothrombotic risk factors

Gleim, Scott; Stitham, Jeremiah; Tang, Wai Ho; Martin, Kathleen A.; Hwa, John

doi:10.1007/s00018-012-0982-9

Cited by 38 publications

(37 citation statements)

References 303 publications

(287 reference statements)

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“…However, oxylipid metabolism does not seem to follow a simple mass‐action rule, at least when measured globally in serum, and our findings are in agreement with a previous report. In a murine inflammatory model, a single high dose of aspirin significantly lowered plasma levels of COX‐, LOX‐, and CYP‐derived AA metabolites 13, 40. The authors concluded that the COX, LOX, and CYP pathways “do not proceed in a parallel way but communicate in a dynamic manner.” In contrast, Shinde et al14, 41 reported that aspirin significantly decreased TXB2 levels in plasma of healthy volunteers, but not the levels of CYP‐, LOX‐, or AA‐derived metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…Oxylipids have myriad functions that are still being elucidated. Aberrant oxylipid signaling has been shown to lead to a number of pathologies important to cardiovascular disease including hyperlipidemia, hypertension, thrombosis, and hemostasis 13. For example, coronary artery disease patients have higher plasma levels of CYP‐mediated AA metabolites (namely, the oxylipids epoxyeicosatrienoic acid) 14.…”

Section: Introductionmentioning

confidence: 99%

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Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

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BackgroundWhile aspirin is a well‐established and generally effective anti‐platelet agent, considerable inter‐individual variation in drug response exists, for which mechanisms are not completely understood. Metabolomics allows for extensive measurement of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response.Methods and ResultsWe used a mass‐spectrometry‐based metabolomics platform to investigate the changes in the serum oxylipid metabolome induced by an aspirin intervention (14 days, 81 mg/day) in healthy subjects (n=156). We observed a global decrease in serum oxylipids in response to aspirin (25 metabolites decreased out of 30 measured) regardless of sex. This decrease was concomitant with a significant decrease in serum linoleic acid levels (−19%, P=1.3×10−5), one of the main precursors for oxylipid synthesis. Interestingly, several linoleic acid‐derived oxylipids were not significantly associated with arachidonic‐induced ex vivo platelet aggregation, a widely accepted marker of aspirin response, but were significantly correlated with platelet reactivity in response to collagen.ConclusionsTogether, these results suggest that linoleic acid‐derived oxylipids may contribute to the non‐COX1 mediated variability in response to aspirin. Pharmacometabolomics allowed for more comprehensive interrogation of mechanisms of action of low dose aspirin and of variation in aspirin response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Ellero‐Simatos¹,

Beitelshees

Lewis

et al. 2015

JAHA

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“…One prospective study also found that smoking was not a predictor of PDPH . In addition, we studied whether diabetes and hypertension that were also known as risk factors for thrombosis could influence the development of PDPH or not , but they also did not predict PDPH.…”

Section: Discussionmentioning

confidence: 97%

Does lumbar puncture at night prevent post-dural puncture headache?

Park

Shin

et al. 2014

Acta Neurol Scand

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“…Dietary cholesterol intake is known to induce an elevation of lipids and stimulate oxidative stress, which lead or promote the action of pro-inflammatory signaling cascades [16], [17], [18]. On the other hand, the bioactive nature of some foods like onion ( Allium cepa L.), which is an important dietary source of antioxidant and anti-inflammatory compounds, has been related to the modulation of such cascades and could reduce the production of pro-inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia

et al. 2017

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The levels and roles of lipid mediators can be modified in response to nutritional stimuli. The aim of this study was to investigate shifts in oxylipin and sphingolipid profiles stimulated by a hypercholesterolemic (HC) diet along with the modulating effects of onion introduced as an antioxidant functional ingredient characterized in the diet (HCO). Oxylipin and sphingolipid profiles were determined in plasma and tissues from Wistar rats using LC-MS/MS. Plasma ω-3 and ω-6 PUFA-derived oxylipins decreased in rats after 7 weeks of HC feeding, but did not evidence a further shift with HCO diet. Onion ingredient supplementation modulated the hepatic concentrations of prostaglandins and enhanced ω-3 oxylipins in the liver of HCO-fed rats relative to the HC group. The HC diet induced shifts in plasma sphingolipids, increasing sphingoid bases, dihydroceramides and ceramides, whilst the sphingomyelin, hexosylceramide and lactosylceramide families decreased. The HCO diet modified some HC diet-induced changes in sphingolipids in liver and spleen tissue. Onion supplementation effected changes in lipid mediator levels in diet-induced hypercholesterolemic Wistar rats. The potential of onion as regulator of pro-inflammatory mediators, and possible enhancer of pro-resolution pathways, warrants further study of the interaction of functional ingredients with bioactive lipid mediators and their potential impact on inflammation, oxidative stress and organ dysfunction.

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An eicosanoid-centric view of atherothrombotic risk factors

Cited by 38 publications

References 303 publications

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Oxylipid Profile of Low‐Dose Aspirin Exposure: A Pharmacometabolomics Study

Does lumbar puncture at night prevent post-dural puncture headache?

New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia

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