Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia

Abstract

The purpose of this study was to determine whether increased serum soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF) levels in pre-eclampsia are related to the clinical features and laboratory parameters of the patients, including markers of inflammation, endothelial activation and injury, oxidative stress and trophoblast debris. A total of 54 pre-eclamptic patients, 58 healthy pregnant and 52 healthy non-pregnant women were involved in this case-control study. Serum sFlt-1 and PlGF levels were measured by electrochemiluminescence immunoassay. Serum levels of sFlt-1 and PlGF were significantly higher in pre-eclamptic patients and healthy pregnant women than in healthy non-pregnant women. In addition, pre-eclamptic patients had significantly higher sFlt-1 levels and significantly lower PlGF concentrations compared with healthy pregnant women. According to the subgroup analyses, sFlt-1 levels were significantly higher in severely pre-eclamptic patients than in those with mild pre-eclampsia, whereas pre-eclamptic patients with fetal growth restriction or preterm onset of the disease had significantly lower PlGF concentrations compared with those without intrauterine growth restriction or with a disease onset at term. In the pre-eclamptic group, there were significant positive correlations between serum sFlt-1 levels and systolic and diastolic blood pressure, serum levels of blood urea nitrogen and creatinine, as well as plasma levels of von Willebrand factor antigen, fibronectin and cell-free fetal DNA. Furthermore, serum PlGF concentrations of pre-eclamptic patients showed significant positive correlations with gestational age at disease onset and delivery, as well as with fetal birth weight, and significant inverse correlations with levels of blood urea nitrogen, creatinine and fibronectin. In conclusion, increased serum sFlt-1 and decreased PlGF levels are associated with blood pressure, renal and endothelial dysfunction, trophoblast deportation, as well as with a shorter duration of pregnancy, fetal growth restriction, the severity and preterm onset of the disease in pre-eclampsia. These findings indicate the central role of an angiogenic imbalance in the pathogenesis of this pregnancy-specific disorder.

The obstetric syndromes: clinical relevance of placental hormones

“…Moreover, the importance of the utility of sFlt-1/PlGF ratio has also been recently shown in identifying the risk for imminent delivery, as in serum of patients with PE/HELLP, its increased concentration is associated with the risk of delivering within 7 days [43]. Similar results were also shown by Molvarec et al, who highlight the decreased PlGF concentration in women with PE associated with IUGR and PTD, focusing on the symbiotic role between the three diseases [44].…”

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

“…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].…”

“…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]…”

Plasma level of hydroxysteroid (17-β) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fms-like tyrosine kinase 1/placental growth factor ratio

“…3,7,9,[15][16][17][18][19][20][21][22][23][24][25] In this study, we also revealed that a new and automated electrochemiluminescence immunoassay for plasma sFlt-1 and PlGF levels at 19-25 weeks of gestation had potential predictive power for predicting all PE. In our current study, the LR þ of the plasma level of the sFlt-1/PlGF ratio at 19-25 weeks for predicting all PE was 4.2, whereas in the previous study using an ELISA kit (R&D Systems, Minneapolis, MN, USA), the LR þ of the serum level of the sFlt-1/PlGF ratio at 19-25 weeks for predicting all PE was 4.7 (Ohkuchi et al 3 ).…”