Treatment of inflammatory diseases by selective eicosanoid inhibition: a double-edged sword?

Yedgar, Saul; Krimsky, Miron; Cohen, Yuval; Flower, Roderick J.

doi:10.1016/j.tips.2007.07.005

Cited by 50 publications

(46 citation statements)

References 68 publications

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“…5 Biosynthesized from arachidonic acid precursor through transcellular biosynthesis in a temporal and spatial manor, lipoxin A 4 possesses potent antiinflammatory and pro-resolution actions that have been demonstrated in a multitude of acute and chronic inflammatory conditions. 5 In the presence of aspirin, a 15R epimer of lipoxin A 4 (ATL) is generated, which, while longer lived than native LXA 4 , shares the potent bioactions of LXA 4 and binds specifically to the lipoxin receptor ALX with high affinity. 18 The tissue distribution profile of ALX shows that in both human and mouse, peripheral leukocytes are a major site of ALX expression, with lower amounts in the spleen and lungs.…”

Section: Discussionmentioning

confidence: 99%

“…3 The acute inflammatory response develops and actively resolves to re-establish homeostasis and involves the local biosynthesis and actions of lipid autacoids. 3 While cyclooxygenase (COX) and lipoxygenase (LOX)-derived lipid mediators such as the prostaglandins and leukotrienes have well-established roles in promoting inflammation, 4 it is now clear that anti-inflammatory and pro-resolving lipid mediators are generated in a temporal and spatial manner to actively turn off inflammation. Among these endogenous pro-resolution mediators are the lipoxins and resolvins.…”

mentioning

confidence: 99%

“…5 Lipoxin A 4 (LXA 4 ) is generated from arachidonic acid through the sequential action of LOX enzymes. Aspirin acetylation of COX-2 gives rise to epimeric lipoxins, termed aspirin-triggered lipoxin (ATL) in the case of LXA 4 , by switching the enzymatic activity from a prostaglandin endoperoxide synthase to a lipoxygenase. 5 We have previously shown that the endothelium participates in transcellular biosynthesis of ATL through the generation and delivery of 15R-hydroxyeicosatetraenoic acid to adhering leukocytes.…”

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confidence: 99%

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Aspirin-Triggered Lipoxin and Resolvin E1 Modulate Vascular Smooth Muscle Phenotype and Correlate with Peripheral Atherosclerosis

Spite

Owens

et al. 2010

The American Journal of Pathology

193

191

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Atherosclerosis is a chronic inflammatory disease of the vessel wall. Recent evidence suggests that chronic vascular inflammation ensues as an imbalance between pro-and anti-inflammatory mediators. Recently identified lipid mediators (eg, lipoxins and resolvins) play active roles in promoting the resolution of inflammation. Alterations in vascular smooth muscle cell (VSMC) phenotype, which manifest as a loss of contractile protein expression and increased proliferation and migration, are prominent mechanistic features of both atherosclerosis and restenosis following various interventions (eg, angioplasty and bypass grafting). We sought to determine whether human atherosclerosis is associated with a "resolution deficit" and whether lipoxins and resolvins influence VSMC phenotype. Here we report that plasma levels of aspirin-triggered lipoxin are significantly lower in patients with symptomatic peripheral artery disease than in healthy volunteers. Both aspirintriggered lipoxin and resolvin E1 block platelet-derived growth factor-stimulated migration of human saphenous vein SMCs and decrease phosphorylation of the platelet-derived growth factor receptor-␤. Importantly, receptors for aspirin-triggered lipoxin and resolvin E1 (ALX and ChemR23, respectively) were identified in human VSMCs. Overall, these results demonstrate that stimulatory lipid mediators confer a protective phenotypic switch in VSMCs and elucidate new functions for these mediators in the regulation of SMC biology. These results also suggest that peripheral artery disease is associated with an inflammation-resolution deficit and highlight a potential therapeutic opportunity for the regulation of vascular injury responses. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Aspirin-Triggered Lipoxin and Resolvin E1 Modulate Vascular Smooth Muscle Phenotype and Correlate with Peripheral Atherosclerosis

Spite

Owens

et al. 2010

The American Journal of Pathology

193

191

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“…Activated cPLA2 then releases arachidonic acid -the source of prostaglandins, leukotrienes and thromboxanes. These eicosanoids mediate the classical features of inflammation and promote a wide range of diseases from chronic inflammation, allergy, cardiovascular disease and obesity to cancer and more 3,25 . Eicosanoids 26 and S1P 11,27 act extracellularly through GPCRs, and function in conjunction with chemokines, cytokines and histamine.…”

Section: Box 2 | Intracellular Signalling By Phosphoinositidesmentioning

confidence: 99%

Lipid signalling in disease

Wymann

Schneiter

2008

Nat Rev Mol Cell Biol

1,140

906

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“…The cell damage associated with inflammation causes cell membranes to release arachidonic acid (Levick et al, 2007). Arachidonic acid undergoes two metabolic pathways: the cyclooxygenase (COX) pathway involving cyclooxgenase-1 (COX-1) and cyclooxgenase-2 (COX-2) to produce the prostaglandins and thromboxanes (Rainsford, 2007); and the lipoxygenase (LOX) pathway, involving 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX) and , to produce the leukotrienes and hydroperoxy fatty acids (Samuelsson et al, 1987;Yedgar et al, 2007).…”

Section: Introductionmentioning

confidence: 99%