Changes in circulating concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor measured by automated electrochemiluminescence immunoassays methods are predictors of preeclampsia

Leaños‐Miranda, Alfredo; Campos-Galicia, Inova; Isordia‐Salas, Irma; Rivera-Leaños, Roxana; Romero-Arauz, Juan Fernando; Ayala-Mendez, Jose Antonio; Ulloa‐Aguirre, Alfredo

doi:10.1097/hjh.0b013e328357c0c9

Cited by 48 publications

(35 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have recently reported that altered placental long-chain polyunsaturated fatty acids may alter the membrane lipid fatty acid composition, leading to the increased release of sFlt-1 in circulation; furthermore, we have also discussed the possibility that the maternal sFlt-1/PlGF ratio may be predictive of PE. 15,41 This is in line with findings reported in recent studies 22,42 but is in contrast to other studies indicating that in early pregnancy, this ratio is not useful for the prediction of PE. 20 The cord plasma VEGF levels in this study were lower in women with PE compared with normotensive women and this supports the findings of previous studies.…”

Section: Discussionsupporting

confidence: 90%

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

et al. 2014

View full text Add to dashboard Cite

Our earlier studies of preeclampsia (PE) at delivery have demonstrated the alteration of one carbon cycle, reduced placental omega 3 fatty acids, altered circulating levels of angiogenic factors and differential placental gene-specific methylation patterns of angiogenic factors. This study was undertaken to examine changes in the levels of angiogenic factors and angiotensin II type 1 receptor autoantibodies (AT1-AAs) throughout gestation, from early pregnancy until delivery, in women with PE and to examine their association with cord angiogenic factors, blood pressure and infant weight. A total of 81 pregnant women (46 normotensive and 35 with PE) were followed at three different time points during pregnancy: 16-20 weeks (T1), 26-30 weeks (T2) and at the time of delivery (T3). The plasma levels of angiogenic factors and AT1-AAs were determined in the maternal and cord plasma by commercial enzyme-linked immunosorbent assay kits. Maternal plasma levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were lower (P<0.05 for both), whereas soluble fms-like tyrosine kinase-1 (sFlt-1; P<0.05) and the sFlt-1/PlGF ratio (P<0.01) were higher in early pregnancy in the PE group. Maternal plasma AT1-AA levels were higher (P<0.05) at T2 in women with PE. Cord plasma VEGF and soluble kinase insert domain receptor (sKDR) levels were lower (P<0.01 and P<0.05, respectively), whereas AT1-AA levels were higher (P<0.05) in the PE group. Maternal plasma VEGF levels in early pregnancy were positively associated with systolic blood pressure, whereas the sFlt-1/PlGF ratio at T2 was negatively associated with infant weight in the PE group. Low levels of proangiogenic factors (VEGF and PlGF) and high levels of AT1-AAs and antiangiogenic factors (sFlt-1 and sFlt-1/PlGF ratio) are present in the maternal circulation during early gestation in women with PE.

show abstract

Section: Discussionsupporting

confidence: 90%

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Our results are consistent with previous reports and provide further support to the notion that alterations of these angiogenic factors not only do occur in women with preeclampsia but also that these biochemical abnormalities become more pronounced as the severity of the disease increases, particularly when preeclampsia occurs preterm. [5][6][7][8] We also showed that higher urinary PRL levels and ALT indicates alanine amino transferase; AST, aspartate amino transferase; LDH, lactate deshydrogensase; PlGF, placental growth factor; PRL, prolactin; sEng, soluble endoglin; and sFlt-1, soluble fms-tyrosine kimase-1. P value is given only for significant differences: *vs women with mild preeclampsia or †vs women with severe preeclampsia after application of appropriate statistical tests.…”

Section: Discussionmentioning

confidence: 75%

“…4,5 Higher circulating concentrations of soluble vascular endothelial growth factor receptor-1 (also referred as soluble fms-like tyrosine kinase-1 [sFlt-1]) and soluble endoglin (sEng), and lower concentrations of placental growth factor (PlGF), are present at the time of diagnosis of preeclampsia and have been associated with an elevated risk to develop this condition for several weeks before the onset of the clinical manifestations. [5][6][7][8] On the other hand, prolactin (PRL), which is physiologically elevated during normal pregnancy, has many effects beyond reproduction and lactation, including an eminent role in angiogenesis and antiangiogenesis. [9][10][11] The major circulating PRL isoform is a 23-kDa single-chain polypeptide (monomeric PRL), which comprises up to 90% of total PRL.…”

mentioning

confidence: 99%

Circulating Angiogenic Factors and Urinary Prolactin as Predictors of Adverse Outcomes in Women With Preeclampsia

et al. 2013

Self Cite

View full text Add to dashboard Cite

Preeclampsia is a multisystemic pregnancy-specific disease characterized by endothelial dysfunction.1 This condition develops in 5% to 8% of all pregnant women and remains a major cause of maternal and perinatal morbidity and mortality worldwide. 2,3 Although the cause of this pregnancy-specific syndrome is unclear, accumulating evidence suggests that preeclampsia results from an imbalance between placental proangiogenic and antiangiogenic factors that result in maternal vascular endothelium damage. 4,5 Higher circulating concentrations of soluble vascular endothelial growth factor receptor-1 (also referred as soluble fms-like tyrosine kinase-1 [sFlt-1]) and soluble endoglin (sEng), and lower concentrations of placental growth factor (PlGF), are present at the time of diagnosis of preeclampsia and have been associated with an elevated risk to develop this condition for several weeks before the onset of the clinical manifestations.5-8 On the other hand, prolactin (PRL), which is physiologically elevated during normal pregnancy, has many effects beyond reproduction and lactation, including an eminent role in angiogenesis and antiangiogenesis. 9-11The major circulating PRL isoform is a 23-kDa single-chain polypeptide (monomeric PRL), which comprises up to 90% of total PRL.12 This full-length PRL stimulates angiogenesis. In contrast, 16-and 14-kDa PRL fragments that result from proteolytic cleavage of monomeric PRL have antiangiogenic effects. 9,13 We and others have shown that urinary PRL excretion and its antiangiogenic PRL fragments are elevated in preeclamptic women, increasing with the severity of the disease and the occurrence of adverse outcomes.11,14 Furthermore, the antiangiogenic PRL fragments are also increased in serum, amniotic fluid, and placenta of preeclamptic women.14,15 These data suggest that PRL might contribute to the pathogenesis of preeclampsia and that perturbation of this angiogenesis pathway may have an important impact on the development of clinical manifestations and complications.Despite the establishment of criteria and guidelines for diagnosis of preeclampsia, its severity, and management, these criteria have been unable to predict adverse maternal outcomes.Abstract-Preeclampsia is characterized by an imbalance in angiogenic factors. Urinary prolactin (PRL) levels and its antiangiogenic PRL fragments have been associated with disease severity. In this study, we assessed whether these biomarkers are associated with an increased risk of adverse maternal and perinatal outcomes in preeclamptic women. We studied 501 women with preeclampsia attended at a tertiary care hospital. Serum concentrations of soluble fmslike tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), as well as urinary PRL levels, were measured by enzymed-linked immunosorbent assay. Antiangiogenic PRL fragments were determined by immunoblotting. The risk for any adverse maternal outcome and for having a small-for-gestational-age infant was higher among women with sFlt-1/PlGF ratios, sEng...

show abstract

“…This finding suggests that sFlt-1 may be a good marker for earlyonset PE. Previous studies have supported the hypothesis that an earlier onset of PE corresponds with higher sFlt-1 levels [26,27]. However, there are still some discrepancies in the reported sFlt-1 protein levels between studies.…”

Section: Discussionmentioning

confidence: 89%

A Role of sFlt-1 in Oxidative Stress and Apoptosis in Human and Mouse Pre-Eclamptic Trophoblasts1

Jiang

Zou

et al. 2015

Biology of Reproduction

View full text Add to dashboard Cite

Pre-eclampsia (PE) is a hypertensive disorder that occurs during pregnancy, and is a multifactorial disease. The antiangiogenic factor, soluble fms-like tyrosine kinase 1 (sFlt-1), has been reported to be important in the pathogenesis of PE, but the mechanism of its involvement remains unknown. To test the effects of sFlt-1 on pregnancy, we injected pregnant mice with exogenous mouse sFlt-1. After 18 days of gestation, higher blood pressure, proteinuria, and histological differences were observed compared with controls. Mitochondrial swelling inside the trophoblast cells in the placenta of sFlt-1-treated pregnant mice was observed by electron microscopy, which suggested a role of sFlt-1 in oxidative stress in trophoblasts in PE. Furthermore, apoptosis markers were upregulated in sFlt-1-treated mice. In conclusion, sFlt-1 appears to play a role in oxidative stress, which promotes apoptosis of trophoblasts. This may be an important mechanism in the development of PE.

show abstract

Changes in circulating concentrations of soluble fms-like tyrosine kinase-1 and placental growth factor measured by automated electrochemiluminescence immunoassays methods are predictors of preeclampsia

Abstract: Changes in circulating concentrations of PlGF, sFlt-1, and in the sFlt-1/PlGF ratio precede the onset of preeclampsia. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested at preterm or term.

Cited by 48 publications

References 31 publications

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

Circulating Angiogenic Factors and Urinary Prolactin as Predictors of Adverse Outcomes in Women With Preeclampsia

A Role of sFlt-1 in Oxidative Stress and Apoptosis in Human and Mouse Pre-Eclamptic Trophoblasts1

Contact Info

Product

Resources

About