Maternal serum Netrin-1 levels as a new biomarker of preeclampsia

Aim: The aim of this study was to investigate whether the Netrin-1 levels in maternal serum was associated with the presence of preeclampsia (PE).

Methods: Total 72 patients, including 28 normal pregnant women and 44 patients with PE, were included in this study. Maternal serum Netrin-1 concentration was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Maternal serum Netrin-1 levels were detected statistically higher in preeclamptic group than control group (p?p?>?0.05).

Conclusion: Maternal serum Netrin-1 has a potential to be a new marker for the detection of PE.     

Maternal serum inhibin-A for predicting preeclampsia

Objective.?To evaluate the use of late first trimester maternal serum inhibin-A concentrations in prediction of preeclampsia.

Design.?Prospective study.

Setting.?Tanta University Hospital.

Methods.?All cases (327) were subjected to complete history taking, clinical and ultrasound examination, CBC, liver function tests, estimation of 24?h urine protein and venous blood samples were taken during the late first trimester for estimation of serum level of inhibin-A.

Results.?First trimester maternal serum inhibin-A concentrations were significantly higher in women who subsequently develop preeclampsia than the corresponding values in healthy matched control pregnant women.

Conclusions.?Measurement of inhibin-A during late first trimester of pregnancy can be useful in the prediction of preeclampsia.     

Maternal serum autotaxin levels in early- and late-onset preeclampsia

Purpose: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital.

Methods: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients. The control group was composed of 32 healthy pregnant patients.

Results: The mean autotaxin levels were 1.16 ± 0.97 and 0.7 ± 0.35 ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin levels were significantly higher in early-onset preeclampsia group compared with late-onset preeclampsia group. Autotaxin levels were found to be significantly higher in preeclamptic patients compared with control group. Serum autotaxin levels showed a significant positive correlation with maternal systolic, diastolic blood pressures and uric acid levels.

Conclusion: Autotaxin might be a promising marker for detecting early-onset preeclampsia. However, further studies are necessary to confirm this hypothesis.     

Use of serum and urinary soluble sFlt-1 and PLGF in the diagnosis of preeclampsia

Objective: Preeclampsia (PE) is a disorder of pregnancy marked by hypertension and proteinuria with no known treatment aside from pregnancy termination. The pathogenesis of PE is poorly understood, but is thought to originate in the placenta. We assessed the value of measuring serum and urinary soluble deformylase-like tyrosine kinase receptor 1 (sFlt-1), a known target of placental factors, and placental growth factor (PLGF), a key placental signaling molecule, in the diagnosis of PE.

Methods: Eighty patients with PE were classified as either exhibiting mild (44 cases) or severe (36 cases) symptoms of PE. Forty normal pregnant women were selected as controls. Serum and urinary PLGF and sFlt-1 levels, along with the ratio of sFlt-1 to PLGF, were compared across groups.

Results: Serum and urinary sFlt-1 and sFlt-1/PLGF ratios in severe PE patients were significantly higher than those in the mild PE group, and measurements from mild PE patients were significantly higher than controls (all P values <0.01). The serum and urinary PLGF levels in severe PE patients were significantly lower than mild PE patients, and mild PE patients had significantly lower PLGF levels than controls (all P values <0.01). As expected, serum sFlt-1 and PLGF levels and ratios were highly correlated with urinary sFlt-1 and PLGF levels and ratios.

Conclusions: The severity of PE was closely correlated with these measurements, suggesting that they may be useful tools in the diagnosis and evaluation of PE.     

Predisposition to superimposed preeclampsia in women with chronic hypertension: endothelial,renal, cardiac,and placental factors in a prospective longitudinal cohort

ABSTRACT

Objective

To assess the contribution of maternal and placental factors to the development of superimposed preeclampsia in women with chronic hypertension.     

ABCA1基因R219K与血脂及子痫前期易感性的相关性研究

目的探讨福建省汉族人群三磷腺苷结合转运子A1基因（ABCA1）R219K单核苷酸多态性（SNP）和子痫前期（preeclampsia）及其血脂水平的关联性。方法研究对象621例,包括对照组316例,子痫前期病例组305例。采用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）法鉴定ABCA1基因外显子区R219K单核苷酸多态性并测定血脂水平。结果 ABCA1基因R219K位点K等位基因频率和RK＋KK基因型频率在子痫前期病例组明显降低,差异有高度统计学意义P〈0.001）。子痫前期病例组内RK＋KK基因型患者血清甘油三酯（TG）浓度低于RR基因型,而HDL-C浓度刚好相反,差异有高度统计学意义（P〈0.001）。结论福建省汉族人群ABCA1基因R219K中,K等位基因可能是子痫前期的独立的保护因子,其机制可能是通过提高血液中HDL-C水平,降低TG水平,从而降低了子痫前期合并血脂代谢紊乱的风险性。     

Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia

Background: 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.

Objective: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.

Methods: 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^TM Human Cancer Biomarker Panels 1 and 2.

Results: 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.

Conclusion: 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.     

Maternal serum AMP-activated protein kinase levels in mild and severe preeclampsia

Objective: To investigate Phosphorylated adenosine monophosphate activated protein kinase (AMPK) levels in healthy pregnant women and pregnant women with preeclampsia (PE).

Methods: Twenty-eight women with mild-PE, 22 with severe-PE, and 30 normotensive controls were included in this cross-sectional study. The serum AMPK levels of these patients were analyzed. The patients were followed up to delivery.

Results: No statistically significant difference was found between the groups for age, gravida, parity, and gestational age at the time the blood samples were obtained (p?>?.05). No significant difference between the group with mild-PE and the control group was found, while in the severe-PE group, serum AMPK levels were significantly higher relative to both the mild-PE and control groups (p?p?Conclusions: Serum AMPK was higher in patients with severe-PE compared with healthy pregnant women and patients with PE without severe features so it might be a new biomarker for the prediction of disease and its severity.     

Maternal serum glycodelin levels in preeclampsia and its relationship with the severity of the disease

Purpose: Preeclampsia, in which insufficient trophoblastic invasion is thought to be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin is a regulator of immunosuppression, fertilization, implantation, and placentation. Because of its inhibitory effects on trophoblastic activity, trophoblast invasion is disturbed when its levels alter. We aimed to analyze serum glycodelin levels in preeclampsia and evaluate whether it correlates with the severity of disease.

Methods: This is a prospective case–control study conducted in a research and training hospital between March and September 2016. In this study, a total of 55 preeclamptic and 65 healthy pregnants were included. Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild. Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent assay.

Results: Glycodelin levels were higher in preeclamptic group as compared with controls (71.38?±?22.78 versus 42.32?±?12.28?ng/ml, p?p?r?=?0.637 and r?=?0.714, respectively, p?r?=?0.369, p?=?.006 and r?=?0.377, p?=?.005) and proteinuria (r?=?0.342, p?=?.011). Moreover, it was correlated with birth weights and gestational age at delivery (r?=??0.386, p?=?.004 and r?=??0.394, p?=?.003, respectively). The role of glycodelin to diagnose preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under the curve for glycodelin is 0.897 with p?53.64?ng/ml. Moreover, area under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p?83.97?ng/ml.

Conclusion: Glycodelin may be a promising marker in predicting the presence and severity of preeclampsia.     

Maternal serum sestrin 2 levels in preeclampsia and their relationship with the severity of the disease

Objective: To investigate sestrin 2 (SESN2) levels in preeclampsia (PE) cases and uncomplicated pregnancies.

Methods: Cross-sectional study including 26 pregnant women with PE, 24 with severe-PE, and 30 randomly selected healthy pregnant women.

Results: The mean arterial pressure, severe proteinuria, number of HELLP syndrome cases, and serum SESN2 levels in the severe PE group were significantly higher than those in the other groups (p < 0.001, p < 0.001, p = 0.006, and p = 0.004, respectively). Negative correlation was found between the birth interval (r = ?.262, p = 0.019) and the SESN2 level.

Conclusion: SESN2 seems to play a role in the pathophysiology of PE, especially in severe PE cases.     

The expression of placental soluble fms-like tyrosine kinase 1 in mouse placenta varies significantly across different litters from normal pregnant mice

Objective: Gene expression studies often pool tissues from multiple placentas when using animal models of preeclampsia without accounting for the potential confounders of litter origin or pup sex. We aimed to determine whether placental gene expression differs based on sex or litter. Methods: We examined the differential expression of soluble fms-like tyrosine kinase 1 (Flt-1) using 35 pups from six normal pregnant mice. Results: Expression of sFlt-1 (p?=?0.003) was significantly different between litters but not between sexes (p?=?0.17). Conclusions: These findings highlight the importance of adequate sampling from multiple litters in expression studies when using animal models in clinical research.     

雌激素和孕激素对子宫内膜基质细胞血小板反应素-1表达的影响

目的探讨雌二醇(E2)和孕酮(P4)对体外培养的人子宫内膜基质细胞(ES细胞)血小板反应素-1(TSP-1)表达的影响。方法 2007年12月至2008年10月在北京协和医院用不同浓度的E2及P4处理体外培养的ES细胞一定时间(研究组),提取细胞RNA和蛋白,分别用Northern blot和Western blot方法比较研究组和未用激素刺激的对照组之间TSP-1 mRNA和蛋白水平的差异。结果 E2能抑制ES细胞TSP-1的表达,与对照组相比,用10nmol/L的E2处理ES细胞后,其TSP-1 mRNA和蛋白水平分别下降(47.6±6.5)%(P<0.05)和(49.0±8.6)%(P<0.05);高浓度P4(10μmol/L)能诱导ES细胞表达TSP-1,与对照组相比,10μmol/L的P4处理ES细胞后,其TSP-1 mRNA和蛋白水平分别是对照组的(2.1±0.4)倍(P<0.05)和(2.3±0.6)倍(P<0.05);低浓度(10nmol/L)P4能增强E2对TSP-1蛋白表达的抑制作用,但对其mRNA的表达无明显影响。结论雌激素和孕激素能有差别地调节ES细胞TSP-1的表达,这一发现为子宫内...     

Relationship between hypoxia and downstream pathogenic pathways in preeclampsia

Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1α (HIF-1α) ¸ a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies. We first confirmed a 2.5-fold upregulation of HIF-1α protein in placentas from preeclampsia when compared to non-hypertensive controls. Consistent with prior studies, we also observed a 10-fold upregulated sFlt1 mRNA and 2-fold upregulated miR-210 in preeclamptic tissue. Interestingly, while sFlt1 mRNA correlated with miR-210 in preeclampsia (R² = 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1α expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia.     

Increased serum heme oxygenase-1 levels as a diagnostic marker of oxidative stress in preeclampsia

Objective: To evaluate the utility of serum biomarkers in the diagnosis of preeclampsia (PE) and also investigate possible correlation with pathogenesis of PE. Methods: Maternal serum concentrations of heme oxygenase-1 (HO1) and N-myc downstream-regulated gene 1 (NDRG1) were measured at 27–34 weeks of gestation in a case–control study of 33 pregnant women diagnosed with PE and in 43 normotensive pregnant women without proteinuria. The Mann–Whitney U test and Spearman's correlation were used for statistical analysis. Results: The median serum HO1 level was found to be significantly higher in the PE group [76.7?ng/ml (23.4–445.7)] than control group [55.9?ng/ml (3.7–354.3)] (p?=?0.006). Positive correlation was found between HO1 levels with presence of PE (r?=?0.316, p?=?0.005). There was no significant difference in NDRG1 values between the two groups (p?=?0.226). Conclusions: Serum HO1 levels were found to be increased in patients with PE compared with normotensive pregnant women.