Placental Growth Factor Concentrations Research Articles

Women with endometriosis have increased levels of placental growth factor in the peritoneal fluid compared with women with cystadenomas.

To assess the release of placental growth factor (PlGF) into peritoneal fluid in women with and without endometriosis, we measured its concentration with reference to disease stage, the presence of red endometriotic lesions and the phase of menstrual cycle. Surgery was scheduled in the proliferative or secretory phase of the menstrual cycle for 59 women with (n = 35) or without (n = 24) endometriosis. The latter group comprised women undergoing surgery for ovarian cystadenomas. PlGF concentrations in the peritoneal fluid were measured using an enzyme-linked immunosorbent assay. PlGF concentration in the peritoneal fluid was markedly elevated in the endometriosis patients (median 189 pg/ml, interquartile range 84-475 pg/ml) as compared with the controls (88 pg/ml, 41-213 pg/ml; P < 0.001), especially in women with red lesions. Significantly greater values during the secretory phase of the menstrual cycle as compared with the proliferative phase were observed in both the control (cystadenoma) group (P < 0.05) and the endometriosis group (P < 0.001). Our findings suggest that production of PlGF is sensitive to the cyclic changes in ovarian steroids and may contribute to the pathogenesis of endometriosis, especially that of red lesions, by promoting neovascularization.

Maternal plasma levels of cytokines in normal and preeclamptic pregnancies and their relationship with diastolic blood pressure and fibronectin levels.

To determine the plasma concentrations of placental growth factor (PLGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), soluble tumor necrosis factor alpha receptor (sTNFp55), interleukin-2 receptor (IL-2R), and interleukins 6 and 10 (IL-6, IL-10) in normotensive and preeclamptic women, and to evaluate the correlations between these cytokines and the diastolic blood pressure and fibronectin levels. A prospective case-control study. Thirty-five women with preeclampsia were compared with 34 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained and plasma levels of PLGF, VEGF, TGF-beta1, sTNFp55, IL-2R, IL-6 and IL-10 were measured by an enzyme-linked immunoassay and fibronectin by a radial immundiffusion technic. In preeclampsia PLGF and VEGF levels were significantly lower, and TGF-beta1, sTNFp55, IL-2R, IL-6 and IL-10 levels were significantly higher than in normotensive pregnancy (p < 0.001). The plasma levels of PLGF and VEGF significantly decreased, whereas TGF-beta1, sTNFp55, IL-2R, IL-6 and IL-10 levels significantly increased with the increments in diastolic blood pressure and fibronectin levels (p < 0.001). Altered concentrations of various cytokines might explain the shallow placentation and endothelial cell dysfunction described in preeclampsia. The clinical severity of preeclampsia seems to correlate with the severity of the cytokine abnormalities.

The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction.

Placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) are involved in placental angiogenesis through interactions with the VEGFR-1 and VEGFR-2 receptors. The placenta of pregnancies whose outcome is fetal growth restriction (FGR) are characterized by abnormal angiogenic development, classically associated with hypoxia. The present study evaluated the near-term expression of this growth factor family in an ovine model of placental insufficiency-FGR, in relationship to uteroplacental oxygenation. Compared to controls, FGR pregnancies demonstrated a 37% increase in uterine blood flow (FGR vs. control, 610.86+/-48.48 vs. 443.17+/-37.39 ml min(-1) (kg fetus)(-1); P<0.04), which was associated with an increased maternal uterine venous PO2 (58.13+/-1.00 vs. 52.89+/-1.26 mmHg; P<0.02), increased umbilical artery systolic/diastolic ratio (3.90+/-0.33 vs. 2.12+/-0.26, P<0.05), and fetal hypoxia (arterial PO2; 12.79+/-0.97 vs. 18.65+/-1.6 mmHg, P<0.005). Maternal caruncle PlGF mRNA was increased in FGR (P<0.02), while fetal cotyledon VEGF mRNA was reduced (P<0.02). VEGFR-1 mRNA was also reduced in FGR fetal cotyledon (P<0.001) but was not altered in caruncle tissue. Immunoblot analysis of PlGF and VEGF demonstrated single bands at 19,000 and 18,600 Mr, respectively. Caruncle PlGF concentration was increased (P<0.04), while cotyledon VEGF was decreased (P<0.05) in FGR placentae. The data establish that uterine blood flow is not reduced in relationship to metabolic demands in this FGR model and that the transplacental PO2 gradient is increased, maintaining umbilical oxygen uptake per unit of tissue. Furthermore, these data suggest that an increased transplacental gradient of oxygen generates changes in angiogenic growth factors, which may underline the pathophysiology of the post-placental hypoxic FGR.

Second-Trimester Maternal Serum Placental Growth Factor and Vascular Endothelial Growth Factor for Predicting Severe, Early-Onset Preeclampsia

In Brief OBJECTIVE To determine whether alterations in second-trimester maternal serum cytokine concentrations can identify women at risk for developing severe, early-onset preeclampsia. METHODS Patients with severe preeclampsia requiring delivery prior to 34 weeks (n = 20) were each matched by gestational age, gravidity, parity, and sample freezing time with three healthy controls who delivered at term (n = 60). By using second-trimester maternal sera originally collected for fetal aneuploidy screening, the concentrations of placental growth factor, vascular endothelial growth factor, granulocyte colony-stimulating factor, endothelin-1, and human chorionic gonadotropin were compared between patients and controls. Logistic regression analysis was used to estimate odds ratios for high versus low (median split) cytokine concentrations with respect to the development of severe, early-onset preeclampsia. Receiver operating characteristic (ROC) curves based on a second logistic regression, using actual cytokine values, were plotted to illustrate reciprocal impact on sensitivity and specificity. RESULTS Placental growth factor and vascular endothelial growth factor levels were significantly lower in patients than in controls. No significant differences were observed for the other cytokines. The odds ratios (with 95% confidence intervals) were 15.54 (3.29, 73.40) for vascular endothelial growth factor and 4.20 (1.35, 13.06) for placental growth factor. Receiver operating characteristic analysis of placental growth factor and vascular endothelial growth factor confirmed that both were useful in discriminating between patients and controls. Models combining both vascular endothelial growth factor and placental growth factor provided the best performance for identifying patients at risk for developing severe, early-onset preeclampsia, according to both odds ratios and ROC analyses. CONCLUSION Combined analysis of placental growth factor and vascular endothelial growth factor is potentially useful as a tool for early identification of patients at risk for developing severe, early-onset preeclampsia. Combined analysis of second-trimester maternal serum placental growth factor and vascular endothelial growth factor levels can identify patients at risk for developing severe, early-onset preeclampsia.

Second-trimester maternal serum placental growth factor and vascular endothelial growth factor for predicting severe, early-onset preeclampsia.

To determine whether alterations in second-trimester maternal serum cytokine concentrations can identify women at risk for developing severe, early-onset preeclampsia. Patients with severe preeclampsia requiring delivery prior to 34 weeks (n = 20) were each matched by gestational age, gravidity, parity, and sample freezing time with three healthy controls who delivered at term (n = 60). By using second-trimester maternal sera originally collected for fetal aneuploidy screening, the concentrations of placental growth factor, vascular endothelial growth factor, granulocyte colony-stimulating factor, endothelin-1, and human chorionic gonadotropin were compared between patients and controls. Logistic regression analysis was used to estimate odds ratios for high versus low (median split) cytokine concentrations with respect to the development of severe, early-onset preeclampsia. Receiver operating characteristic (ROC) curves based on a second logistic regression, using actual cytokine values, were plotted to illustrate reciprocal impact on sensitivity and specificity. Placental growth factor and vascular endothelial growth factor levels were significantly lower in patients than in controls. No significant differences were observed for the other cytokines. The odds ratios (with 95% confidence intervals) were 15.54 (3.29, 73.40) for vascular endothelial growth factor and 4.20 (1.35, 13.06) for placental growth factor. Receiver operating characteristic analysis of placental growth factor and vascular endothelial growth factor confirmed that both were useful in discriminating between patients and controls. Models combining both vascular endothelial growth factor and placental growth factor provided the best performance for identifying patients at risk for developing severe, early-onset preeclampsia, according to both odds ratios and ROC analyses. Combined analysis of placental growth factor and vascular endothelial growth factor is potentially useful as a tool for early identification of patients at risk for developing severe, early-onset preeclampsia.

Longitudinal serum concentrations of placental growth factor: Evidence for abnormal placental angiogenesis in pathologic pregnancies

Objective: Complicated pregnancies demonstrate abnormal decidual and placental villous vasculature. We examined maternal concentrations of vascular endothelial growth factor and placental growth factor in normal pregnancies and in pregnancies that were complicated by isolated idiopathic small-for-gestational-age (SGA) newborn infants, preeclampsia alone, or preeclampsia with SGA newborn infants at the time of clinical disease and before the onset of clinical signs. Study Design: Serum vascular endothelial growth factor and placental growth factor were measured by enzyme-linked immunosorbent assay in cross-sectional and longitudinal cohorts of pregnant nulliparous women. The results were compared by Wilcoxon tests or a mixed-models method, respectively. Results: In the cross-sectional study, serum placental growth factor was reduced in abnormal pregnancy relative to control subjects (SGA newborn infants, 18 [P = .04]; preeclampsia, 20; or preeclampsia with small- for-gestational-age newborn infants, 11 [P = .0001]) as early as 15 to 19 weeks of gestation in preeclampsia with SGA newborn infants. Vascular endothelial growth factor was <30 pg/mL in all serum specimens from pregnant women. Conclusion: We postulate that decreased placental growth factor production results in abnormalities of placental angiogenesis through direct and indirect effects on other vasculotropic growth factors. (Am J Obstet Gynecol 2003;188:177-82.)

Increased placental growth factor (PlGF) concentrations in children and adolescents with obesity and the metabolic syndrome.

Childhood obesity and the Metabolic Syndrome (MetS) are associated with an increased risk for early onset endothelial dysfunction and atherosclerosis. Placental growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in atherosclerosis by stimulating angiogenesis and atherogenic migration of monocytes/macrophages into the arterial wall. The aim of this study was to investigate differences in circulating PlGF concentrations between children with obesity/metabolic syndrome and non-obese children. We have previously shown increased high-sensitivity troponin (hs-TnT) concentrations in children with MetS from the same cohort. Fifty-seven obese (49 without and 8 with MetS) and 25 non-obese children (controls) were assessed at the Childhood Obesity Clinic of our Department. Obesity was defined using the IOTF criteria. MetS was defined based on the IDF criteria. PlGF was measured using electrochemiluminescence methodology. Mean PIGF concentrations of obese children were significantly higher (p=0.048) compared with those of the controls. Analysis of the three groups, the οbese (without MetS), the MetS and the control, demonstrated a significant difference in PlGF concentrations (p=0.035). Subgroup analysis revealed increased PlGF concentrations in children with the MetS compared to the controls (p=0.009). Troponin had a significant positive correlation with PlGF overall (p=0.003) and in the obese group (p=0.046). Increased serum concentrations of PlGF, a biomarker of angiogenesis, are found in obese children with the MetS compared to non-obese controls, whereas PlGF correlated positively with troponin. Longitudinal studies may reveal the prognostic role of this biomarker in the progression of atherosclerosis in obese children with the MetS.

Reductions of vascular endothelial growth factor and placental growth factor concentrations in severe preeclampsia

Objective: The aim of this study was to determine whether plasma concentrations of vascular endothelial growth factor and placental growth factor are altered in women with severe preeclampsia. Study Design: We performed a case-control study to compare plasma concentrations of vascular endothelial growth factor and placental growth factor between women with severe preeclampsia and normotensive women admitted for delivery. Twenty-one women with severe preeclampsia were matched for gestational age and ethnicity with 21 normotensive women. Vascular endothelial growth factor and placental growth factor concentrations were measured with a specific antigen-capture enzyme-linked immunosorbent assay. Results: Women with severe preeclampsia demonstrated significantly lower plasma concentrations of both vascular endothelial growth factor (6.36 ± 3.96 pg/mL vs 18.65 ± 5.98 pg/mL; P <.0001) and placental growth factor (138 ± 119 pg/mL vs 531 ± 340 pg/mL; P <.0001) than did women with normotensive pregnancy. Logistic regression analysis showed an independent association between plasma vascular endothelial growth factor concentration and plasma placental growth factor concentration and preeclampsia. Conclusion: Patients with severe preeclampsia had decreased maternal serum concentrations of both vascular endothelial growth factor and placental growth factor. (Am J Obstet Gynecol 2000;183:1554-7.)

Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia.

To compare serum levels of angiogenic growth factors vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and angiogenin in pre-eclamptic women and matched controls. Retrospective analysis of -70 degrees C stored serum of women who developed pre-eclampsia and matched controls. Department of Gynaecology and Obstetrics, St Elisabeth Hospital, Curaçao, Netherlands Antilles. Thirty women with pre-eclampsia and 30 normotensive controls matched for age and gestation. VEGF and PIGF serum levels were significantly lower in pre-eclamptic pregnancies, compared with controls (VEGF 0.31 +/- 1.20 vs 18.30 +/- 24.97 pg/mL, P = 0.0004; PlGF 54.19 +/- 32.05 vs 497.95 +/- 340.51 pg/mL, P < 0.0001). Matched couple analysis showed VEGF serum concentrations to be lower in the majority of pre-eclamptic women and PlGF concentrations to be lower in all pre-eclamptic women. Angiogenin serum levels showed no statistical significant difference between pre-eclamptic pregnancies and controls (523.68 +/- 367.55 vs 670.41 +/- 251.54 ng/mL, P = 0.058), with matched couple analysis showing no clear pattern. Decreased serum levels of VEGF and PIGF characterise, and therefore seem to be of importance during (the development of), pre-eclampsia. This selective deficit of angiogenic growth factors might in part explain the shallow placentation found in this pregnancy complication.