The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia

Hagmann, Henning; Thadhani, Ravi; Benzing, Thomas; Karumanchi, S. Ananth; Stepan, Holger

doi:10.1373/clinchem.2011.169094

Cited by 119 publications

(68 citation statements)

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“…Considerable effort has been made to identify biomarkers that could predict women who will develop preeclampsia [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Although markers of systemic inflammation [79,80] and endothelial dysfunction [81][82][83][84][85][86][87][88] in maternal blood have been associated with preeclampsia, their prognostic performance for the identification of patients with preeclampsia prior to diagnosis has been disappointing [79][80][81]83,[89][90][91].…”

Section: Introductionmentioning

confidence: 99%

“…Preeclampsia [63][64][65][66][67]69,70,72,[92][93][94][95][96][97][98][99][100][101][102][103], as well as other obstetrical syndromes [46,[104][105][106][107][108][109][110][111][112][113][114][115][116][117][118], is characterized by an anti-angiogenic state. Plasma concentrations of the angiogenic factor, placental growth factor (PlGF), are decreased [69,70,92,93,96,[100][101][102], and the anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 [sVEGFR-1] and soluble endoglin [sEng]) are elevated both prior to [67,72,[119]…”

Section: Introductionmentioning

confidence: 99%

“…Plasma concentrations of the angiogenic factor, placental growth factor (PlGF), are decreased [69,70,92,93,96,[100][101][102], and the anti-angiogenic factors (soluble vascular endothelial growth factor receptor-1 [sVEGFR-1] and soluble endoglin [sEng]) are elevated both prior to [67,72,[119][120][121][122][123][124][125] and at the time of diagnosis [94,95,[97][98][99]. Moreover, the concentrations of these factors can be used to predict the outcome of the disease in patients presented to the obstetrical triage area [73,75,126,127].…”

Section: Introductionmentioning

confidence: 99%

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Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis. Methods: This cross-sectional study included women with preeclampsia (n ¼ 106) and women with an uncomplicated pregnancy (n ¼ 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte. Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p50.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p ¼ 0.7 and p ¼ 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho ¼ 0.72 and 0.63; each p50.0001), and negatively with PlGF (Spearman's Rho ¼ À0.56, p50.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (537 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors. Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the uteroplacental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic f...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Stampalija

Chaiworapongsa

Romero

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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“…Early termination of pregnancy is one of the main treatments for the patients with severe preeclampsia (Haddad et al 2010). The efficient diagnosis and prediction method for preeclampsia is still unavailable (Hagmann et al 2012). The high efficient and safe way for precise diagnosis of preeclampsia is needed.…”

Section: Introductionmentioning

confidence: 99%

Low Serum Levels of ABCA1, an ATP-Binding Cassette Transporter, Are Predictive of Preeclampsia

Liu

Zhang

Min³

et al. 2015

Tohoku J. Exp. Med.

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Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria, but the exact cause of preeclamptic hypertension remains unknown. ATP-binding cassette subfamily A member 1 (ABCA1) reverses cholesterol transport and eliminates excess cholesterol from tissues, whereas higher levels of cholesterol may lead to hypertension. Thus, ABCA1 affects the blood lipid profile. We have hypothesized that serum ABCA1 levels may influence the onset of hypertension and increase the risk of preeclampsia. To test this hypothesis, we measured serum ABCA1 levels in 50 normal pregnancies, 36 preeclamptic pregnancies, and 24 small-for-gestational-age (SGA) pregnancies during three trimesters. We also measured the concentrations of serum ABCA1 in non-pregnant women (n = 60), showing its normal ranges of 0.16 to 0.52 ng/ml. Importantly, the serum levels of ABCA1 were similar among non-pregnant women, normal pregnancies and SGA pregnancies. In contrast, the serum ABCA1 levels were significantly lower in preeclamptic pregnancies (0.06 ± 0.03 ng/ml) than those in non-pregnant women, and normal and SGA pregnancies (P < 0.05). Low serum ABCA1 levels were associated with the increases in the concentrations of blood lipid (low density lipoprotein cholesterol, total cholesterol and triglycerides) and with the decrease in the concentration of high-density lipoprotein cholesterol (P < 0.01), all of which may contribute to the onset of hypertension and eventually preeclampsia. Moreover, the preeclamptic pregnancy was diagnosed with high sensitivity from the nulliparous pregnancies if the cutoff value for serum ABCA1 was 0.06 ng/ml. Thus, low serum levels of ABCA1 are predictive of preeclampsia.

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“…In addition, the relationship of first trimester PAPP-A to serial levels of placental growth factor (PlGF) and serial ratios of sFlt-1 to PlGF were also explored, as studies have shown that PlGF is significantly lower in preeclampsia [9] and the ratio of sFlt-1/PlGF is also significantly elevated in preeclampsia [10,11], prior to the onset of clinical signs.…”

Section: Introductionmentioning

confidence: 99%

732: First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia

Saxena

Seely

Rich‐Edwards

et al. 2012

American Journal of Obstetrics and Gynecology

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The Promise of Angiogenic Markers for the Early Diagnosis and Prediction of Preeclampsia

Cited by 119 publications

References 91 publications

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Low Serum Levels of ABCA1, an ATP-Binding Cassette Transporter, Are Predictive of Preeclampsia

732: First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia

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