Gene expression in chorionic villous samples at 11 weeks' gestation from women destined to develop preeclampsia

Farina, Antonio; Sekizawa, Akihiko; Sanctis, Paola De; Purwosunu, Yuditiya; Okai, Takashi; Hyun, Dong Choon; Kang, Jung Hoon; Vicenzi, Claudia; Tempesta, A.; Wibowo, Noroyono; Valvassori, Luisa; Rizzo, Nicola

doi:10.1002/pd.2109

Cited by 92 publications

(75 citation statements)

References 32 publications

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“…The expression levels of Flt-1, ENG and VEGF in CVS tissue obtained from pregnant women who later developed PE were higher, and those of PlGF and HO-1 were lower, than those of normal pregnancies. 16 These findings indicate that the up-regulation of anti-angiogenic factors and the down-regulation of anti-oxidant factors have already occurred in first-trimester trophoblasts, 16 and that the alterations could be evaluated by the analysis of cellular RNA. All of these findings support the hypothesis that some mRNA expression of Flt-1, ENG, PlGF, VEGF and HO-1 is derived from circulating trophoblasts, and that the alteration of these mRNA levels may reflect mRNA alterations associated with the pathogenesis of PE in the placenta.…”

Section: Discussionmentioning

confidence: 99%

“…The results revealed that the expression levels of Flt-1, ENG, VEGF and transforming growth factor-b1 (TGFb1) were significantly higher in the CVS tissues from pregnant women who later developed PE, whereas the levels of PlGF, HO-1 and superoxide dismutase (SOD) were lower. 16 These findings suggest that the genes associated with angiogenesis and reduced anti-oxidant stress play crucial roles in the pathogenesis of PE, and that the measurement of the expression of these factors in maternal blood may enable the prediction of the onset of PE.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22] The investigation was designed as a prospective cohort study in early pregnant women (gestational weeks [15][16][17][18][19][20] who visited the Department of Obstetrics and Gynaecology, University of Indonesia, Cipto Mangunkusumo National Hospital, Indonesia from mid-2005 to 2006. Singleton pregnant women without any pre-existing medical diseases at screening or antenatal complications at the time of blood drawing were invited to participate in the cohort.…”

Section: Subjectsmentioning

confidence: 99%

“…The in vivo alteration of gene expression has been observed in the first-trimester trophoblasts from pregnant women destined to develop PE later, confirming this hypothesis. 16 In this study, tissue samples of villous trophoblasts at the time of fetal karyotype analysis were collected prospectively through chorionic villous sampling (CVS), and the mRNA expression of these genes was assessed. The results revealed that the expression levels of Flt-1, ENG, VEGF and transforming growth factor-b1 (TGFb1) were significantly higher in the CVS tissues from pregnant women who later developed PE, whereas the levels of PlGF, HO-1 and superoxide dismutase (SOD) were lower.…”

Section: Introductionmentioning

confidence: 99%

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Prediction of pre‐eclampsia by an analysis of placenta‐derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation

Sekizawa

Purwosunu

Farina

et al. 2010

BJOG

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Objective A panel of cellular mRNA markers was used to predict the occurrence of pre-eclampsia in pregnant women at 15-20 weeks of gestation.Design Prospective cohort study.Setting The Department of Obstetrics and Gynaecology, University of Indonesia, Cipto Mangunkusumo National Hospital, Indonesia.Sample Peripheral blood samples from asymptomatic pregnant women.Methods Among 660 women, 62 developed pre-eclampsia at later gestation (pre-eclampsia group) and each case was matched with five controls. Therefore, the RNA expression levels in the cellular component of maternal blood in 62 women with pre-eclampsia were compared with those in 310 controls.Main outcome measures The cellular RNA expression levels of genes related to angiogenesis and oxidative stress were compared between pre-eclampsia and control groups. A receiver operating characteristic (ROC) curve was used to analyse the sensitivity of each available marker. A logistic regression analysis was performed to calculate the odds for each woman to be classified as a case.Results The univariate ROC analysis identified soluble vascular endothelial growth factor receptor-1 (Flt-1) and endoglin (ENG) as the markers with the highest sensitivity. The best multivariate model was obtained by combining Flt-1, ENG, placental growth factor (PlGF) and parity. The relative ROC curve yielded a sensitivity of 66% at a 10% 1 ) specificity rate with an area under the curve of 0.884 (P < 0.001).Conclusion A panel of cellular mRNA markers in maternal blood can predict the development of pre-eclampsia long before clinical onset.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prediction of pre‐eclampsia by an analysis of placenta‐derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation

Sekizawa

Purwosunu

Farina

et al. 2010

BJOG

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“…HO is expressed by trophoblasts, and its inhibition has been shown to result in defective trophoblast invasion in vitro (20). Human studies have also shown that levels of Hmox are decreased in patients with preeclampsia (21)(22)(23)(24)(25)(26)(27). Furthermore, the addition of sera from patients with preeclampsia led to decreased levels of Hmox in vitro (28).…”

Section: Heme Oxygenase Pathwaymentioning

confidence: 99%

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps

Prasanna

Brima

et al. 2016

CJASN

512

328

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Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a selflimited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

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MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6

Zhang

Pan

et al. 2018

Molec Gen & Gen Med

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BackgroundThe remodeling of maternal spiral artery following embryo implantation, which relies on well‐regulated trophoblast functions, is a pivotal process to ensure a successful pregnancy. Low‐density lipoprotein receptor‐related protein 6 (LRP6) and microRNAs (miRNAs, miRs) are suggested to be involved in angiogenesis and several vascular diseases; however, their functions in the control of trophoblast remain elusive. We therefore aimed to examine the roles of LRP6 and miR‐590‐3p in the regulation of trophoblast during the remodeling of maternal spiral artery.MethodsHTR‐8/SVneo cell, a trophoblast cell line, was utilized to study the effects of LRP6 and miR‐590‐3p on apoptosis, cell proliferation, migration, invasion, as well as tube formation. Expression of angiogenic factors placental growth factor (PlGF), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and activities of canonical Wnt/β‐catenin signaling pathway, which were implicated in the process of artery remodeling, were also examined.ResultsMiR‐590‐3p directly targeted 3′ untranslated region (3′‐UTR) of LRP6 mRNA and repressed LRP6 expression, which in turn inhibited proliferation, migration, invasion, as well as tube formation, and resulted in apoptosis in HTR‐8/SVneo cells. Further, inhibition of LRP6 through miR‐590‐3p significantly suppressed the expression of PlGF, MMPs, and VEGF and reduced the activation of Wnt/β‐catenin signaling pathway.ConclusionMicroRNAs‐590‐3p may inhibit trophoblast‐dependent maternal spiral artery remodeling, via both trophoblast invasion and endovascular formation, by repressing LRP6.

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Gene expression in chorionic villous samples at 11 weeks' gestation from women destined to develop preeclampsia

Cited by 92 publications

References 32 publications

Prediction of pre‐eclampsia by an analysis of placenta‐derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation

Prediction of pre‐eclampsia by an analysis of placenta‐derived cellular mRNA in the blood of pregnant women at 15–20 weeks of gestation

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

MicroRNA‐590‐3p inhibits trophoblast‐dependent maternal spiral artery remodeling by repressing low‐density lipoprotein receptor‐related protein 6

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