Angiogenic growth factors in maternal and fetal serum in pregnancies complicated with intrauterine growth restriction

Borras, Dolores; Perales‐Puchalt, Alfredo; Sacedón, Nerea Ruiz; Perales, Alfredo

doi:10.3109/01443615.2013.834304

Cited by 20 publications

(14 citation statements)

References 7 publications

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“…This is a very interesting find as decreased invasion, decreased PlGF expression, and increased sflt-1 are all hallmarks present during PE and IUGR. 22,[34][35][36] In contrast, when PlGF was added to the Rapamycin treated cells, sflt-1 mRNA expression was restored to control levels. This suggests a role for mTOR phosphorylation and the regulation of PlGF signaling in the invasion of trophoblast cells.…”

Section: Discussioncontrasting

confidence: 51%

Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells

Knuth

Liu

Nielsen

et al. 2014

American J Rep Immunol

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Section: Discussioncontrasting

confidence: 51%

Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells

Knuth

Liu

Nielsen

et al. 2014

American J Rep Immunol

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“…Previous studies have investigated the relationships between sFlt-1 and/or PlGF and late-onset FGR, but most have utilized methods not readily translated into clinical practice for a general antenatal population. These methods include placental rather than plasma protein analysis [24]; multi-modality integrated models [25, 26]; prior ultrasound diagnosis of SGA [27–33]; and investigation confined to cases of preterm infants [32]. Our large cohort specifically enabled us to compare the utility of sFlt-1, PlGF, and their ratio, in all cases of a SGA infant as well as in a ‘SGA only’ cohort, actively removing the impact of participants with concurrent preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

“…Our results add clarity where previous findings have been inconsistent. Prior to this study, elevated sFlt-1 had been associated with FGR in some animal [34], and human [31, 32, 35, 36] studies with cases of preeclampsia excluded, but not in others [18, 33]. The large numbers in our study and the ability to test levels in both ‘All SGA’ and ‘SGA only’ cohorts have allowed us to confidently define sFlt-1 as a biomarker more specific to preeclampsia, rather than FGR.…”

Section: Discussionmentioning

confidence: 99%

Assessing the sensitivity of placental growth factor and soluble fms-like tyrosine kinase 1 at 36 weeks’ gestation to predict small-for-gestational-age infants or late-onset preeclampsia: a prospective nested case-control study

MacDonald

Tran

Kaitu’u-Lino

et al. 2018

BMC Pregnancy Childbirth

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BackgroundFetal growth restriction is a disorder of placental dysfunction with three to four-fold increased risk of stillbirth. Fetal growth restriction has pathophysiological features in common with preeclampsia. We hypothesised that angiogenesis-related factors in maternal plasma, known to predict preeclampsia, may also detect fetal growth restriction at 36 weeks’ gestation. We therefore set out to determine the diagnostic performance of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1:PlGF ratio, measured at 36 weeks’ gestation, in identifying women who subsequently give birth to small-for-gestational-age (SGA; birthweight <10th centile) infants. We also aimed to validate the predictive performance of the analytes for late-onset preeclampsia in a large independent, prospective cohort.MethodsA nested 1:2 case-control study was performed including 102 cases of SGA infants and a matched group of 207 controls; and 39 cases of preeclampsia. We determined the diagnostic performance of each angiogenesis-related factor, and of their ratio, to detect SGA infants or preeclampsia, for a predetermined 10% false positive rate.ResultsMedian plasma levels of PlGF at 36 weeks’ gestation were significantly lower in women who subsequently had SGA newborns (178.5 pg/ml) compared to normal birthweight controls (326.7 pg/ml, p < 0.0001). sFlt-1 was also higher among SGA cases, but this was not significant after women with concurrent preeclampsia were excluded. The sensitivity of PlGF to predict SGA infants was 28.8% for a 10% false positive rate. The sFlt-1:PlGF ratio demonstrated better sensitivity for preeclampsia than either analyte alone, detecting 69.2% of cases for a 10% false positive rate.ConclusionsPlasma PlGF at 36 weeks’ gestation is significantly lower in women who subsequently deliver a SGA infant. While the sensitivity and specificity of PlGF currently limit clinical translation, our findings support a blood-based biomarker approach to detect late-onset fetal growth restriction. Thirty-six week sFlt-1:PlGF ratio predicts 69.2% of preeclampsia cases, and could be a useful screening test to triage antenatal surveillance.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-1992-x) contains supplementary material, which is available to authorized users.

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“…More recent studies by Borras et al (2014) have reported that maternal plasma free VEGF (f-VEGF) and s-Flt-1 were significantly higher in FGR compared with controls and the f-VEGF/sFlt-1 quotient was significantly lower in the FGR group compared with controls. Although the VEGF family has important roles in normal and complicated pregnancies, the current predictive value of the VEGF family as biomarkers appears to be limited to early onset preeclampsia (Andraweera et al, 2012).…”

Section: Downstream Targets Of Homeobox Genesmentioning

confidence: 98%

Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

2014

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Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterized by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation, and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.

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Angiogenic growth factors in maternal and fetal serum in pregnancies complicated with intrauterine growth restriction

Cited by 20 publications

References 7 publications

Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells

Placenta Growth Factor Induces Invasion and Activates p70 during Rapamycin Treatment in Trophoblast Cells

Assessing the sensitivity of placental growth factor and soluble fms-like tyrosine kinase 1 at 36 weeks’ gestation to predict small-for-gestational-age infants or late-onset preeclampsia: a prospective nested case-control study

Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

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