The effect of phosphoramidon on inflammation-mediated preterm delivery in a mouse model

Koscica, Karen L.; Sylvestre, Georges; Reznik, Sandra E.

doi:10.1016/j.ajog.2003.08.021

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…24 Phosphoramidon, however, also inhibits neutral endopeptidase. 28 Therefore another possible mechanism of the effect of phosphoramidon in Figure 5.…”

Section: Discussionmentioning

confidence: 99%

“…24 In addition, we have recently found that treating LPS-stimulated pregnant mice with 6-alkoxy substituted-3-carboxybenzyl-N-benzyl-quinol-4-ones, designed and synthesized as novel endothelin receptor A antagonists by our group, results in decreased incidence of premature delivery. 25 In the current work, we present biochemical, pharmacological, and molecular evidence that ET-1 has a critical function in an animal model simulating inflammation-associated premature delivery.…”

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confidence: 99%

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The Endothelin-Converting Enzyme-1/Endothelin-1 Pathway Plays a Critical Role in Inflammation-Associated Premature Delivery in a Mouse Model

Wang

Yen

Chen

et al. 2008

The American Journal of Pathology

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Premature delivery occurs in 12% of all births and accounts for nearly half of long-term morbidity. Current therapeutic approaches to preterm delivery are ineffective and present serious risks to both mother and fetus. The single most common cause of preterm birth is infection. Previous in vitro investigations have shown that endothelin-1 (ET-1) is induced by inflammatory cytokines and that it increases myometrial smooth muscle tone. Furthermore, we have previously shown that both the endothelin-converting enzyme-1 (ECE-1) inhibitor, phosphoramidon, as well as a novel ET-1 receptor A antagonist synthesized by our group, control premature delivery in a mouse model of inflammation-associated preterm delivery. In the current work, we show that levels of both ET-1 and ECE-1 are increased in gestational tissues in E16.5 mice induced to deliver prematurely after lipopolysaccharide administration. We also show that premature delivery is controlled by treatment with the selective endothelin receptor A antagonist BQ-123 in a dose-dependent manner. Finally, we show here for the first time that premature delivery can be controlled using RNA silencing, by hydrodynamic transfection of E15 mice with ECE-1 RNAi. Taken together, these data support a critical role for the ECE-1/ET-1 system in inflammation-associated premature delivery. The ability to control premature delivery by antagonizing or silencing the ECE-1/ET-1 system offers a novel approach to an unmet clinical need.

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“…24 Phosphoramidon, however, also inhibits neutral endopeptidase. 28 Therefore another possible mechanism of the effect of phosphoramidon in Figure 5.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Endothelin-Converting Enzyme-1/Endothelin-1 Pathway Plays a Critical Role in Inflammation-Associated Premature Delivery in a Mouse Model

Wang

Yen

Chen

et al. 2008

The American Journal of Pathology

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“…We reported in 2004 that inhibition of endothelin-converting enzyme-1 (ECE-1), which colocalizes with ET-1 in the placenta [66], controls PTD in a mouse model of infection-associated PTL [67]. Subsequently, we have shown that ECE-1 is upregulated in our mouse model of PTL and that PTD is controlled with the ET A receptor antagonist BQ-123 and with silencing of ECE-1 mRNA [68] (Figure 2).…”

Section: The Endothelinsmentioning

confidence: 99%

The Matrix Metalloproteases and Endothelin‐1 in Infection‐Associated Preterm Birth

Olgun

Reznik

2010

Obstetrics and Gynecology International

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Preterm birth (PTB) is clinically defined as any delivery which occurs before the completion of 37 weeks of gestation, and is currently the most important problem in obstetrics. In the United States, PTB accounts for 12-13% of all live births, and, with the exception of fetuses suffering from anomalies, is the primary cause of perinatal mortality. While the risk factors for PTB are numerous, the single most common cause is intrauterine infection. As there is currently no FDA-approved therapy for infection-associated PTB, understanding the pathogenesis of preterm labor (PTL) and delivery should be given high priority. The matrix metalloproteinases (MMPs) are a family of enzymes that have been implicated in normal parturition as well as infection-triggered rupture of membranes and preterm birth. Several lines of evidence also suggest a role for endothelin-1 (ET-1) in infection-associated preterm delivery. This paper focuses on the evidence that the MMPs and ET-1 act in the same molecular pathway in preterm birth.

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“…It has been suggested that at least 40% of all premature deliveries occur to mothers with intrauterine infection, and that gestational age is inversely related to the frequency of intrauterine infections (2). Considerable evidence suggests that the proinflammatory cytokine-prostaglandin cascade plays a central role in the pathogenesis of infection-associated premature delivery (3,4).…”

Section: Introductionmentioning

confidence: 99%

Prevention of Inflammation-Associated Preterm Birth by Knockdown of the Endothelin-1-Matrix Metalloproteinase-1 Pathway

Wang

Yen

Chen

et al. 2010

Mol Med

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Premature delivery occurs in 12% of all births, accounts for nearly half of neonatal morbidity and is increasing in frequency. Current therapeutic approaches to preterm delivery are ineffective and present serious risks to both the mother and fetus. Although there are multiple factors that contribute to the etiology of preterm birth, the single most common cause is infection. Recently, using cDNA microarray analysis of human placental tissue, we demonstrated that human placental matrix metalloproteinase-1 (MMP-1) is upregulated during labor. In a separate line of investigation, we have shown that blockade of endothelin-1 (ET-1) action through the use of an endothelin-converting enzyme-1 (ECE-1) inhibitor, an established commercially available endothelin receptor antagonist or a novel quinolone-derived endothelin receptor antagonist synthesized by our group also prevents preterm labor and delivery in a mouse model. We have now shown that induction of preterm labor with lipopolysaccharide in our mouse model is associated with increased levels of MMP-1. Furthermore, we showed that silencing the ECE-1/ET-1 pathway by using ECE-1 RNA interference prevents both the onset of preterm labor and upregulation of MMP-1. The data indicate that ET-1 and MMP-1 act in the same molecular pathway in preterm labor.

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The effect of phosphoramidon on inflammation-mediated preterm delivery in a mouse model

Cited by 15 publications

References 16 publications

The Endothelin-Converting Enzyme-1/Endothelin-1 Pathway Plays a Critical Role in Inflammation-Associated Premature Delivery in a Mouse Model

The Endothelin-Converting Enzyme-1/Endothelin-1 Pathway Plays a Critical Role in Inflammation-Associated Premature Delivery in a Mouse Model

The Matrix Metalloproteases and Endothelin‐1 in Infection‐Associated Preterm Birth

Prevention of Inflammation-Associated Preterm Birth by Knockdown of the Endothelin-1-Matrix Metalloproteinase-1 Pathway

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