transforming-growth-factor-alpha and Pre-Eclampsia

Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.. To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.. We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex Pro. The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8-29.8 times in the study population.. The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered.

Topics: Adolescent; Adult; Angiopoietin-2; Biomarkers; Case-Control Studies; Endoglin; ErbB Receptors; Fas Ligand Protein; Female; Hepatocyte Growth Factor; Humans; Interleukin-6; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prognosis; Prolactin; Transforming Growth Factor alpha; Vascular Endothelial Growth Factor A; Young Adult

The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries.. Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunohistochemistry in the trophoblast of placentas (N = 76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides.. Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (p < 0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05).. Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia.

Topics: Adult; Apoptosis; Cell Line, Transformed; Chorionic Villi; Cohort Studies; Down-Regulation; Epidermal Growth Factor; ErbB Receptors; Female; Heparin-binding EGF-like Growth Factor; Humans; Peptide Fragments; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Protein Isoforms; Transforming Growth Factor alpha; Trophoblasts; Young Adult

The aim of these investigations was to study three candidate genes for pre-eclampsia--epidermal growth factor (EGF), transforming growth factor alpha, and angiotensinogen--in pregnant Sinhalese women from Sri Lanka, the first such study undertaken in this ethnic group. Reproducibility of results of genetic association studies of candidate genes for pre-eclampsia has not been consistent across populations. One of the factors that may contribute to such inconsistencies is genetic stratification due to population admixture. We therefore compared the allele frequencies of these candidate genes in healthy Sri Lankan subjects from three ethnic groups--Sinhalese, Sri Lankan Tamils and Moors--and in white Western Europeans.. Allele frequencies were established in 80 subjects from each of four populations (Sinhalese, Sri Lankan Tamils, and Moors in Sri Lanka and white Western Europeans in the U.K.). A further 175 Sinhalese women with pre-eclampsia and 171 normotensive Sinhalese controls were genotyped at eight single nucleotide polymorphisms in the candidate genes.. In all genes haplotype and allele frequencies were comparable within the three Sri Lankan populations, but differed significantly from those in the white Western European population. Consequently cryptic population stratification is unlikely to have significant effects on allele or haplotype frequencies of the genes examined in this case-control study of Sinhalese women which showed a marginal association for EGF haplotypes and genotypes with pre-eclampsia (P = 0.031). This association requires replication in other populations.

Topics: Adult; Angiotensinogen; Epidermal Growth Factor; Female; Haplotypes; Humans; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Sri Lanka; Transforming Growth Factor alpha