angiogenin and Pre-Eclampsia

To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor.. We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index.. 1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group.. Patterns of serum biomarkers vary by high-risk group. These data support the hypothesis that multiple pathogenic pathways lead to the disease recognized clinically as preeclampsia.

Topics: Adult; Antigens, CD; Biomarkers; Chorionic Gonadotropin; Diabetes Mellitus, Type 1; Endoglin; Female; Humans; Hypertension; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Pregnancy Proteins; Pregnancy, Multiple; Progesterone; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor, Type II; Ribonuclease, Pancreatic; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-1; Young Adult

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58-0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

Topics: Adult; Biomarkers; Blood Pressure; Body Mass Index; Cohort Studies; Female; Humans; International Cooperation; Mass Screening; Models, Statistical; Parity; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Proteins; Random Allocation; Ribonuclease, Pancreatic; Risk Factors; Vascular Resistance

We studied the effects of soluble products of the placental tissue from women with normal pregnancy and gestosis on the cytokine secretion by endothelial EA.Hy926 cells. The secretory products of the placental tissue induced the production of angiogenin, bFGF, IL-8, MCP-1, and RANTES by endothelial cells. The secretion of bFGF by EA.Hy926 cells increased, while IL-8 secretion decreased under the effects of factors produced by the placental tissue in gestosis but not in normal pregnancy. This could be aimed at reduction of inflammation intensity in the placental tissue and maintenance of endothelial and trophoblast cells viability.

Topics: Cell Line; Chemokine CCL2; Chemokine CCL5; Cytokines; Endothelial Cells; Female; Fibroblast Growth Factor 2; Humans; Interleukin-8; Placenta; Pre-Eclampsia; Pregnancy; Ribonuclease, Pancreatic; Trophoblasts

To investigate the role of the angiogenic factors, vascular endothelial growth factor (VEGF) and angiogenin in the pathophysiology of preeclampsia and how their concentrations correlate with the severity of the disease and fetal outcome.. A prospective study was carried out on 71 pregnant patients with preeclampsia and 20 pregnant normotensive controls. Maternal serum levels of VEGF and angiogenin were determined in all cases by enzyme immunoassay. Assessment of fetal well-being using the Biophysical Profile Score (BPS), umbilical and uterine artery Doppler velocimetry, and infant birthweight were carried out.. Maternal serum VEGF and angiogenin levels were significantly increased in cases of mild and severe preeclampsia compared to controls. Their increase was positively correlated with elevated systolic and diastolic blood pressure, as well as poor BPS, abnormal Doppler velocimetry, and low birthweight.. Elevated levels of both VEGF and angiogenin could confirm the existence of vascular reactivity and endothelial disturbance in preeclampsia. Measurement of these angiogenic factors in maternal serum may be a useful as biomarkers for the assessment of the severity of the disease and of fetal outcome.

Topics: Adult; Biomarkers; Birth Weight; Blood Flow Velocity; Female; Humans; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prospective Studies; Ribonuclease, Pancreatic; Sensitivity and Specificity; Umbilical Arteries; Uterus; Vascular Endothelial Growth Factor A