Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia

Staff, Anne Cathrine; Brække, Kristin; Harsem, Nina Kittelsen; Lyberg, Torstein; Holthe, Mette R.

doi:10.1016/j.ejogrb.2004.11.015

Cited by 164 publications

(142 citation statements)

References 25 publications

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“…Not surprisingly, our findings of decreased VEGF levels in FGR support the claim that inadequate placentation might be an important aetiological factor in these cases (34). Previous studies have reported increased VEGFR-1 levels in cases with preeclampsia (1,13,(35)(36)(37)(38). It has also been suggested that high levels of sVEGFR-1 inhibits angiogenesis by antagonising the effects of VEGF and PlGF (39,40).…”

Section: Discussionsupporting

confidence: 75%

The effect of Silymarin on VEGF, VEGFR-1 and IL-1α levels in placental cultures of severe preeclamptic women

Kaya

Başer

Kaya

et al. 2014

J Turkish German Gynecol Assoc

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Objective:The purpose of this study was to evaluate the effects of Silymarin on vascular endothelial growth factor (VEGF), soluble VEGF Receptor-1 (sVEGFR-1) and Interleukin-1 alpha (IL-1α) levels in placental tissue samples of severely preeclamptic women. Material and Methods:We conducted an in vitro study in Başkent University Faculty of Medicine, Ankara, Turkey between September 2008 and May 2009. A total of 16 placental tissue samples (8 from severe preeclamptic, and 8 from controls) were analysed. Placental samples were incubated, and VEGF, sVEGFR-1, and IL1-α were measured in culture media using an ELISA kit. The effect of Silymarin on these levels was investigated. Descriptive statistics were initially performed, followed by Mann Whitney U-test and Kruskal-Wallis test to compare means between groups. P values less than 0.05 were considered statistically significant. Results:Eight patients were included in the severe preeclampsia (SP) group, whereas the remaining 8 patients were included in the control group. There were no significant correlations between gestational age and placental VEGF, sVEGFR-1 and IL-1α after 48 or 72 hours of incubation. Basal VEGF levels were lower in the SP group; however, it did not reach statistical significance. sVEGFR-1 and IL-1α levels were also similar between the SP and control groups (p>0.05). After 48 and 72 hours of incubation, sVEGFR-1 levels in Silymarin-added SP and control placental cultures were lower than in the samples without Silymarin addition; however, this difference also did not reach significance. Conclusion:Although we could not demonstrate a significant effect on placental cytokines, considering the role of vasospasm, inflammation, angiogenesis, endothelial cell activation, and oxidative stress in preeclampsia, the potential benefits of Silymarin should be evaluated in future trials with a larger sample size. (J Turk Ger Gynecol Assoc 2014; 15: 30-5) Key words: Severe preeclampsia, placenta, vascular endothelial growth factor, Silymarin Received: 17 August, 2013 Accepted: 30 September, 2013 The effect of Silymarin on VEGF, VEGFR-1 and IL-1α levels in placental cultures of severe preeclamptic women After obtaining informed consent, severe preeclamptic women who underwent caesarean section above 30 weeks of gestation were prospectively included in the study. Severe preeclampsia (SP) was defined as new-onset hypertension and proteinuria in a >20 week pregnant woman with one or more of the following features: 1) severely elevated blood pressure (systolic ≥160 mmHg and/or diastolic ≥110 mmHg) measured at least twice with a 6 hour interval; 2) proteinuria ≥5 gr in 24-hour collected urine or ≥2+ in dipstick test; 3) serum creatinine ≥1.2 mg/dL; 4) oliguria (<400 cc in 24 hours); 5) thrombocytopenia (<100,000/mm 3 ); 6) microangiopathic haemolysis (Lactate dehydrogenase (LDH) ≥600 U/L or uncongugated bilirubin ≥1.2 mg/dL); 7) impaired liver function tests (Aspartate serum transaminase ≥ twice normal); 8) foetal growth restriction (FGR); 9) symptoms of cent...

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Section: Discussionsupporting

confidence: 75%

The effect of Silymarin on VEGF, VEGFR-1 and IL-1α levels in placental cultures of severe preeclamptic women

Kaya

Başer

Kaya

et al. 2014

J Turkish German Gynecol Assoc

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“…5 Some studies could not report any differences between PE and normotensive pregnancies, as most of the concentrations obtained by analysis using a commercially available R&D ELISA kit (R&D Systems, Inc., Minneapolis, MN USA) were below detection limit. 6,7 However, other laboratories using the same kit have reported lower concentrations in established PE as compared with normotensive pregnancies 5,[8][9][10][11] whereas, others 12-14 using the same commercially available assay, actually found free elevated VEGF in established PE group. The differences in study design, limited statistical power and differences in population characteristics such as maternal age, race and ethnicity, severity of PE and gestational age of blood collection are likely to have contributed to the variability of results in various studies.…”

mentioning

confidence: 95%

Angiogenic balance and diagnosis of pre-eclampsia: selecting the right VEGF receptor

Rath

Tripathi

2011

J Hum Hypertens

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“…This state appears to result from an imbalance in the production and circulating concentrations of angiogenic factors such as placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) and anti-angiogenic factors such as soluble VEGF receptor-1 (sVEGFR-1) and soluble endoglin (sEng). Elevated serum and plasma concentrations of sVEGFR-1 and s-Eng have been observed after the diagnosis of PE [1][2][3][7][8][9]11,12,15,18,19,[21][22][23] and before the recognition of clinical disease [4][5][6]10,13,14,16,17,20,30,32].…”

mentioning

confidence: 99%

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

Erez

Romero

Espinoza

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

269

233

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The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age, The Journal of Maternal-Fetal & Neonatal Medicine, 21:5, 279-287, DOI: 10.1080 AbstractIntroduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. Methods. This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n ¼ 201); (2) patients who delivered an SGA neonate (n ¼ 145); and (3) patients who developed PE (n ¼ 56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. Results.(1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively).(2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4....

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Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia

Cited by 164 publications

References 25 publications

The effect of Silymarin on VEGF, VEGFR-1 and IL-1α levels in placental cultures of severe preeclamptic women

The effect of Silymarin on VEGF, VEGFR-1 and IL-1α levels in placental cultures of severe preeclamptic women

Angiogenic balance and diagnosis of pre-eclampsia: selecting the right VEGF receptor

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

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