Serum and plasma determination of angiogenic and anti-angiogenic factors yield different results: The need for standardization in clinical practice

Oggè, Giovanna; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Dong, Zhong; Mittal, Pooja; Vaisbuch, Edi; Mazaki‐Tovi, Shali; González, Juan M.; Yeo, Lami; Hassan, Sonia S.

doi:10.3109/14767050903366119

Cited by 24 publications

(16 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results have been described for other circulating proteins such as VEGF [34]. Also, Oggè G. et al reported comparable levels of PGF in both the plasma and serum of women with a normal pregnancy in the first, second and third trimesters [35] suggesting that the detected difference in our population data may not be ascribable to the source of the PGF measurements. Moreover, in our work, we have found that the environmental and genetic factors have a similar effect in both study samples suggesting that the difference in median levels between the two populations could be related to the effect of other factors able to influence the PGF levels.…”

Section: Discussionsupporting

confidence: 90%

Genetic and Environmental Factors Influencing the Placental Growth Factor (PGF) Variation in Two Populations

et al. 2012

View full text Add to dashboard Cite

Placental Growth Factor (PGF) is a key molecule in angiogenesis. Several studies have revealed an important role of PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation, cardiovascular diseases and inflammatory processes) suggesting its use as a potential therapeutic agent. However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking) on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors: a study sample from two isolated villages in the Cilento region, South Italy (N = 871) and a replication sample from the general Danish population (N = 1,812). A significant difference in PGF mean levels was found between the two cohorts. However, in both samples, we observed a strong correlation of PGF levels with ageing and sex, men displaying PGF levels significantly higher than women. Interestingly, smoking was also found to influence the trait in the two populations, although differently. We have then focused on genetic risk factors. The association between five single nucleotide polymorphisms (SNPs) located in the PGF gene and the plasma levels of the protein was investigated. Two polymorphisms (rs11850328 and rs2268614) were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability.

show abstract

Section: Discussionsupporting

confidence: 90%

Genetic and Environmental Factors Influencing the Placental Growth Factor (PGF) Variation in Two Populations

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The sensitivity and coefficients of variation for these assays are described in Table I. Validation of these assays has been previously described [101]. …”

Section: Methodsmentioning

confidence: 99%

Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes

Adekola

Romero

Chaemsaithong

et al. 2014

The Journal of Maternal-Fetal & Neonatal Medicine

Self Cite

View full text Add to dashboard Cite

Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n = 130); (2) preeclampsia (n = 102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n = 51); (4) FD (n = 49); (5) acute pyelonephritis (AP; n = 35); (6) spontaneous PTL (n = 75); and (7) preterm PROM (n = 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p = 0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p = 0.1), abnormal uterine artery Doppler velocimetry (p = 0.7) or whether diagnosis was made before or after 34 weeks gestational age (p = 0.3); (3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [sVEGFR-1: Spearman rho 0.34, p = 0.001 and sEng: Spearman rho 0.30, p = 0.003]; (4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p = 0.004), as well as uncomplicated pregnancies (p = 0.001); and (5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the “great obstetrical syndromes”; each p > 0.05). Conclusion: Median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy. No significant difference was observed in the median plasma endocan...

show abstract

“…The sensitivity of the assays were as follows: PlGF, 9.52 pg/ml; sVEGFR-2, 19.01 pg/ml; sEng, 0.08 ng/ml and sVEGFR-1, 16.97 pg/ml. The validation of these assays has been described in previous studies [89]. …”

Section: Methodsmentioning

confidence: 99%

Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of preeclampsia

Chaiworapongsa¹,

Romero²,

Savasan³

et al. 2011

The Journal of Maternal-Fetal & Neonatal Medicine

Self Cite

126

104

View full text Add to dashboard Cite

Objective To determine if maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and -2 could identify patients at risk for developing preeclampsia (PE) requiring preterm delivery. Study design Patients presenting with the diagnosis ‘rule out PE’ to the obstetrical triage area of our hospital at <37 weeks of gestation (n=87) were included in this study. Delivery outcomes were used to classify patients into 4 groups: I) patients without PE or those with gestational hypertension (GHTN) or chronic hypertension (CHTN) who subsequently developed PE at term (n=19); II): mild PE who delivered at term (n=15); III): mild disease (mild PE, GHTN, CHTN) who subsequently developed severe PE requiring preterm delivery (n=26); and IV): diagnosis of severe PE (n=27). Plasma concentrations of PlGF, sEng, sVEGFR-1 and -2 were determined at the time of presentation by ELISA. Reference ranges for analytes were constructed by quantile regression in our laboratory (n=180; 1,046 samples). Comparisons among groups were performed using multiples of the median (MoM) and parametric statistics after log transformation. Receiver operating characteristic curves, logistic regression and survival analysis were employed for analysis. Results The mean MoM plasma concentration of PlGF/sVEGFR-1, PlGF/sEng, PlGF, sVEGFR-1 and -2, and sEng in Group III was significantly different from Group II (all p<0.05). A plasma concentration of PlGF/sVEGFR-1 ≤ 0.05 MoM or PlGF/sEng ≤ 0.07 MoM had the highest likelihood ratio of a positive test (8.3, 95% CI 2.8–25 and 8.6, 95% CI 2.9–25, respectively), while that of PlGF ≤0.396 MoM had the lowest likelihood ratio of a negative test (0.08, 95% CI 0.03–0.25). The association between low plasma concentrations of PlGF/sVEGFR-1 (≤0.05 MoM) as well as that of PlGF/sEng (≤ 0.07 MoM) and the development of severe PE remained significant after adjusting for gestational age at presentation, average systolic and diastolic blood pressure, and a history of chronic hypertension [adjusted odds ratio (OR) = 27 (95% CI 6.4–109) and adjusted OR 30 (95% CI 6.9–126), respectively]. Among patients who presented <34 weeks gestation (n=59), a plasma concentration of PlGF/sVEGFR-1 <0.033 MoM identified patients who delivered within 2 weeks because of PE with a sensitivity of 93% (25/27) and a specificity of 78% (25/32). This cut-off was associated with a shorter interval-to-delivery due to PE [hazard ratio = 6 (95% CI 2.5–14.6)]. Conclusions Plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in the obstetrical triage area. These observations support the value of these biomarkers in the clinical setting for the identification of the patient at risk for disease progression requiring preterm delivery.

show abstract

Serum and plasma determination of angiogenic and anti-angiogenic factors yield different results: The need for standardization in clinical practice

Cited by 24 publications

References 83 publications

Genetic and Environmental Factors Influencing the Placental Growth Factor (PGF) Variation in Two Populations

Genetic and Environmental Factors Influencing the Placental Growth Factor (PGF) Variation in Two Populations

Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes

Maternal plasma concentrations of angiogenic/anti-angiogenic factors are of prognostic value in patients presenting to the obstetrical triage area with the suspicion of preeclampsia

Contact Info

Product

Resources

About