Eicosanoids in preeclampsia

Walsh, Scott W.

doi:10.1016/j.plefa.2003.04.010

Cited by 125 publications

(119 citation statements)

References 90 publications

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“…27 Many studies have established that MPs up-regulate COX-2 6,28 ; moreover, preeclamptic women have increased plasma concentrations of substances such as vasoconstrictor eicosanoids. 29 Here we found both up-regulation of COX-2 and higher release of the vasoconstrictor 8-isoprostane on PrMP stimulation compared with CMPs. This suggests that PrMPs directly or indirectly modify the activity of 5-HT with a shift toward substantial vasoconstriction through isoprostanes.…”

Section: Discussionmentioning

confidence: 46%

Shed Membrane Particles from Preeclamptic Women Generate Vascular Wall Inflammation and Blunt Vascular Contractility

Meziani

Tesse

David

et al. 2006

The American Journal of Pathology

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We investigated the role of microparticles in vascular dysfunction of the multisystemic disorder of preeclampsia in women's omental arteries or mouse arteries. Preeclamptic women displayed increased circulating levels of leukocyte-and platelet-derived microparticles compared with healthy pregnant individuals. Microparticles from preeclamptic, but not healthy, pregnant women induced ex vivo vascular hyporeactivity to serotonin in human omental arteries and mouse aortas. Hyporeactivity was reversed by a nitric-oxide (NO) synthase inhibitor and associated with increased NO production. In the presence of a cyclooxygenase (COX)-2 inhibitor, serotonin-mediated contraction was partially reduced in arteries treated with healthy microparticles but was abolished after treatment with preeclamptic microparticles. This was associated with increased 8-isoprostane production. Preeclamptic microparticles induced up-regulation of inducible nitric-oxide synthase and COX-2 expression, evoked nuclear factor-B activation, and enhanced oxidative and nitrosative stress. Interestingly, the microparticles originating most probably from leukocytes were responsible for the COX-2 vasoconstrictor component of preeclamptic microparticles, whereas those of platelet origin were mainly involved in NO release. Moreover, vascular hyporeactivity was observed in arteries taken from mice treated in vivo with preeclamptic microparticles. This study demonstrates pathophysiological relevance and provides a paradoxical effect of preeclamptic microparticles associated with proinflammatory properties on vessels, leading to enhanced NO and superoxide anion levels and counteraction of increased COX-2 metabolites.

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Section: Discussionmentioning

confidence: 46%

Shed Membrane Particles from Preeclamptic Women Generate Vascular Wall Inflammation and Blunt Vascular Contractility

Meziani

Tesse

David

et al. 2006

The American Journal of Pathology

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“…11,12,53 Experimental studies in animals have attempted to determine the role of AA metabolites in response to placental ischemia. Increases in systemic arterial pressure produced by acute placental ischemia in pregnant dogs can be prevented by thromboxane receptor antagonism.…”

Section: Arachidonic Acid Metabolitesmentioning

confidence: 99%

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

2008

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“…Biosynthesis of TxA 2 is increased in preeclampsia, and it relates to the severity of the disease (13). There is some controversy as to whether low-dose aspirin, which preferentially targets PGHS1, may prevent preeclampsia or ameliorate its complications (14)(15)(16)(17). Furthermore, low-dose aspirin differs among tissues in its impact on PGHS1-derived eicosanoids.…”

Section: Introductionmentioning

confidence: 99%

Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition

Chen¹,

Fan²,

Chen³

et al. 2005

J. Clin. Invest.

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Platelet activation is a hallmark of severe preeclampsia, and platelet PGH synthase 1-derived (PGHS1-derived) thromboxane A 2 (TxA 2 ) has been implicated in its pathogenesis. However, genetic disruption of PGHS1 delays parturition. We created hypomorphic PGHS1 (PGHS1 Neo/Neo ) mice, in which the substantial but tissue-dependent variability in the inhibition of PGHS1-derived eicosanoids achieved by low-dose aspirin treatment is mimicked, to assess the relative impact of this strategy on hemostatic and reproductive function. Depression of platelet TxA 2 by 98% in PGHS1 Neo/Neo mice decreased platelet aggregation and prevented thrombosis. Similarly, depression of macrophage PGE 2 by 75% was associated with selectively impaired inflammatory responses. PGF 2α at 8% WT levels was sufficient to induce coordinated temporal oxytocin receptor (OTR) expression in uterus and normal ovarian luteolysis in PGHS1 Neo/Neo mice at late gestation, while absence of PGHS1 expression in null mice delayed OTR induction and the programmed decrease of serum progesterone during parturition. Thus, extensive but tissue-dependent variability in PG suppression, as occurs with low-dose aspirin treatment, prevents thrombosis and impairs the inflammatory response but sustains parturition. PGHS1 Neo/Neo mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function.

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Eicosanoids in preeclampsia

Cited by 125 publications

References 90 publications

Shed Membrane Particles from Preeclamptic Women Generate Vascular Wall Inflammation and Blunt Vascular Contractility

Shed Membrane Particles from Preeclamptic Women Generate Vascular Wall Inflammation and Blunt Vascular Contractility

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition

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