Spiral Artery Remodeling in Preeclampsia Revisited

Burke, Suzanne D.; Karumanchi, S. Ananth

doi:10.1161/hypertensionaha.113.02049

Cited by 39 publications

(24 citation statements)

References 18 publications

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“…472,473,474 Because the molecular basis for this failed remodeling is poorly understood, and because a robust biomarker to predict patients who will become preeclamptic is lacking, it is not yet practical to design targeted therapeutics to correct spiral artery remodeling and prevent PE. However, preeclampsia symptoms do not present until later in pregnancy, and unlike the initiating factors in spiral artery remodeling, the molecular pathways that lead to symptom precipitation are much better understood.…”

Section: Evolving Technologies For Placental Specific Therapeuticmentioning

confidence: 99%

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Ilekis

Tsilou

Fisher

et al. 2016

American Journal of Obstetrics and Gynecology

232

167

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Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles of microRNAs and placental-derived exosomes, as well as messenger RNAs, were also discussed in the context of their use for diagnostics and as drug targets. The workshop discussed the aspect of safety and pharmacokinetic profiles of potential existing and new therapeutics that will need to be determined especially in the context of the unique pharmacokinetic properties of pregnancy, as well as the hurdles and pitfalls of translating research findings into practice. The workshop also discussed novel methods of drug delivery and targeting during pregnancy using macromolecular carriers, such as nanoparticles and biopolymers, to minimize placental drug transfer and hence fetal drug exposure. In closing, a major theme that developed from the workshop was that the scientific community needs to change their thinking of the pregnant women and her fetus as a vulnerable patient population for which drug development should be avoided, but rather thought of as a deprived population in need of more effective therapeutic interventions.

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Section: Evolving Technologies For Placental Specific Therapeuticmentioning

confidence: 99%

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Ilekis

Tsilou

Fisher

et al. 2016

American Journal of Obstetrics and Gynecology

232

167

View full text Add to dashboard Cite

show abstract

“…In humans, the defective invasion of the maternal decidua by fetal EVTs leads to insufficient perfusion of the placenta, resulting in pregnancy complications, such as intrauterine growth restriction, (recurrent) spontaneous abortion, (very) premature birth and preeclampsia [6, 7]. The unique vascular remodeling of the maternal decidua during pregnancy, whereby both fetal and maternal cells play complementary regulatory roles, is a fundamental process for a successful pregnancy [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Human Extravillous Trophoblasts Penetrate Decidual Veins and Lymphatics before Remodeling Spiral Arteries during Early Pregnancy

Iperen

Jong

et al. 2017

PLoS ONE

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In humans, the defective invasion of the maternal endometrium by fetal extravillous trophoblasts (EVTs) can lead to insufficient perfusion of the placenta, resulting in pregnancy complications that can put both mother and baby at risk. To study the invasion of maternal endometrium between (W)5.5–12 weeks of gestation by EVTs, we combined fluorescence in situ hybridization, immunofluorescence and immunohistochemistry to determine the presence of (male) EVTs in the vasculature of the maternal decidua. We observed that interstitial mononuclear EVTs directly entered decidual veins and lymphatics from W5.5. This invasion of decidual veins and lymphatics occurred long before endovascular EVTs remodelled decidual spiral arteries. This unexpected early entrance of interstitial mononuclear EVTs in the maternal circulation does not seem to contribute to the materno-placental vascular connection directly, but rather to establish (and expand) the materno-fetal interface through an alternative vascular route.

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“…Although the etiology of preeclampsia is uncertain, abnormal placentation is believed to play an essential role in the development of this syndrome [3][4][5]. Poor trophoblast migration/invasion associated with impaired remodeling of the spiral arteries have been linked to preeclampsia [6][7][8][9]. Nevertheless, an understanding of the molecular mechanisms underlying the development of preeclampsia remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia

Pan

Wang

et al. 2014

Biochemical and Biophysical Research Communications

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Spiral Artery Remodeling in Preeclampsia Revisited

Cited by 39 publications

References 18 publications

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

Human Extravillous Trophoblasts Penetrate Decidual Veins and Lymphatics before Remodeling Spiral Arteries during Early Pregnancy

miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia

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