Maternal Serum-Soluble Vascular Endothelial Growth Factor Receptor-1 in Early Pregnancy Ending in Preeclampsia or Intrauterine Growth Retardation

“…Our findings are similar to those reported by Wathen et al, who observed a fall of 15% in the serum concentration of sFlt1 from 14 to 19 weeks during normal pregnancy in contrast to increased levels of sFlt1 from 16 to 20 weeks in women with subsequent preeclampsia. 18 Of further interest is the similarity of the measurements from the CPEP trial performed more than 12 years ago and the present MOMS protocol, supporting the use of these assays in samples appropriately stored over long periods of time.…”

Section: Discussionmentioning

confidence: 53%

Sequential Changes in Antiangiogenic Factors in Early Pregnancy and Risk of Developing Preeclampsia

et al. 2007

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Abstract-Concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) increase in maternal blood with the approach of clinical preeclampsia. Although alterations in these circulating antiangiogenic factors herald the signs and symptoms of preeclampsia, in vitro studies suggest they may also play a role in regulating early placental cytotrophoblast functions. Early pregnancy changes in sFlt1 and sEng may thus identify women destined to develop preeclampsia. We performed a nested case-control study of 39 women who developed preeclampsia and 147 contemporaneous normotensive controls each with serum collected in the first (11 to 13 weeks of gestation) and second (17 to 20 weeks) trimesters. Whereas levels of sFlt1 and sEng at 11 to 13 weeks were similar between cases and controls (sFlt1: 3.5Ϯ0.3 ng/mL versus 3.0Ϯ0.1, Pϭ0.14; sEng 6.9Ϯ0.3 ng/mL versus 6.6Ϯ0.2, Pϭ0.37, respectively), at 17 to 20 weeks both were elevated in the women destined to develop preeclampsia (sFlt1: 4.1Ϯ0.5 ng/mL versus 3.1Ϯ0. Key Words: antiangiogenic factors Ⅲ sFlt1 Ⅲ soluble endoglin Ⅲ preeclampsia Ⅲ predictive test P reeclampsia affects 3% to 5% of pregnancies and causes substantial maternal and neonatal morbidity and mortality. 1 Predicting the development of preeclampsia is important both for prevention (when useful preventive measures become available) and for early referral of high risk pregnancies. Measures to predict preeclampsia, however, are not standardized, and currently there are no reliable biomarkers that are routinely measured in the clinic.Recently, our improved understanding of the pathogenesis of preeclampsia 2,3 has raised the possibility that blood levels of antiangiogenic proteins 4,5 might eventually be used to predict this devastating condition. Circulating soluble fmslike tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) have been hypothesized to play a pathogenic role in preeclampsia. Adenoviral overexpression of sFlt1 and sEng induce development of preeclampsia-like illness in rats. 6 Furthermore, alterations in circulating sFlt1 and sEng are noted several weeks preceding clinical signs. 5 Although there is evidence that angiogenic factor alterations may be strongly associated with the development of the clinical preeclampsia, it is surprising that their levels are not dramatically altered during early pregnancy (11 to 18 weeks of gestation) when the abnormal placentation associated with severe premature preeclampsia develops. This led us to hypothesize that sequential angiogenic factor changes from the first to the second trimesters of pregnancy might differ in women destined to develop preeclampsia, explaining the apparent paradox and that these changes could have predictive value. The aim of the present study, therefore, was to measure concentrations of sFlt1 and sEng in paired serum specimens collected in first and second trimesters from women with well-characterized pregnancy outcomes followed prospectively during pregnancy. Methods Study PopulationWe performed a nested case-cont...

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“…The contribution of sVEGFR-1 to the maternal syndrome of preeclampsia is thought to be, at least in part, related to its inhibition of VEGF stimulation of the endothelium-dependent nitric oxide system (through VEGFR-2) [86]. Plasma sVEGFR-1 concentration has been found to be elevated in preeclampsia both prior to [87][88][89][90][91][92][93][94] and after clinical diagnosis [84,87,[95][96][97][98][99]. In contrast, studies of plasma sVEGFR-1 concentration in women with SGA fetuses have yielded conflicting results-either no change [100] or an increase [99].…”

Section: Introductionmentioning

confidence: 99%

Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age

Chaiworapongsa

Romero

Gotsch

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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Objectives. Preeclampsia is considered an anti-angiogenic state. A role for the anti-angiogenic factors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin in preeclampsia has been proposed. Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) has been detected in human plasma, and the recombinant form of this protein has anti-angiogenic activity. There is a paucity of information about maternal plasma sVEGFR-2 concentrations in patients with preeclampsia and those without preeclampsia with small for gestational age (SGA) fetuses. This study was conducted to determine whether: (1) plasma sVEGFR-2 concentration changes throughout pregnancy; and (2) preeclampsia and SGA are associated with abnormalities in the maternal plasma concentration of sVEGFR-2. Study design. This cross-sectional study included non-pregnant women (n ¼ 40), women with normal pregnancies (n ¼ 135), women with an SGA fetus (n ¼ 53), and women with preeclampsia (n ¼ 112). SGA was defined as an ultrasoundestimated fetal weight below the 10 th percentile for gestational age that was confirmed by neonatal birth weight. Plasma concentrations of sVEGFR-2 were determined by ELISA. Results. (1) There was no significant difference in the mean plasma concentration of sVEGFR-2 between non-pregnant women and those with normal pregnancies ( p ¼ 0.8); (2) patients with preeclampsia and those without preeclampsia with SGA fetuses had a lower mean plasma concentration of sVEGFR-2 than that of women with normal pregnancies ( p 5 0.001 for both); and (3) there was no significant difference in the mean plasma concentration of sVEGFR-2 between patients with preeclampsia and those without preeclampsia with SGA ( p ¼ 0.9). Conclusions. Preeclampsia and SGA are associated with low plasma concentrations of sVEGFR-2. One interpretation of the findings is that plasma sVEGFR-2 concentration could reflect endothelial cell function.

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Maternal Serum-Soluble Vascular Endothelial Growth Factor Receptor-1 in Early Pregnancy Ending in Preeclampsia or Intrauterine Growth Retardation

Abstract: Elevated sVEGFR-1 concentrations at 16-20 wk gestation precede the clinical manifestations of preeclampsia. By neutralizing VEGF, sVEGFR-1 may contribute to inadequate placental vascularization.

Cited by 108 publications

References 26 publications

Role of Soluble FMS-Like Tyrosine Kinase (SFLT-1) /Placental Growth Factor (Plgf) Ratio as Prognostic Marker for Cases of Preeclampsia

Role of Soluble FMS-Like Tyrosine Kinase (SFLT-1) /Placental Growth Factor (Plgf) Ratio as Prognostic Marker for Cases of Preeclampsia

Sequential Changes in Antiangiogenic Factors in Early Pregnancy and Risk of Developing Preeclampsia

Low maternal concentrations of soluble vascular endothelial growth factor receptor-2 in preeclampsia and small for gestational age

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