简介：AbstractPreeclampsia (PE) is a principal cause of maternal and newborn mortality that poses financial and physical burdens to tens of thousands of families each year. Unfortunately, there is no effective management to arrest the progression of this disease unless delivery. Therefore, standardized management or preventive treatments are needed urgently. PE is closely associated with placental hypoxia, which increases the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) as well as soluble endoglin (sEng) into the maternal circulation. Metformin has been found to inhibit those anti-angiogenic factors so it might be a candidate to prevent or treat PE. Women who are diagnosed with gestational diabetes mellitus (GDM) are more likely to have complications of hypertension or PE, so this review aims to demonstrate that the application of metformin in GDM might prevent the onset or progression of PE complicated with GDM.

简介：AbstractPreeclampsia is a progressive, multi-system disorder of pregnancy associated with morbidity and mortality on both the mother and the fetus. Currently, research is directed at identifying early biomarkers of preeclampsia in order to predict its occurrence. This is important because it helps understand the pathophysiology of the disease, and thus, promises new treatment modalities. Although a clear understanding of the pathogenesis of PE remains elusive, the currently most accepted theory suggests a two-stage process. The first stage results in inadequate remodeling of the spiral arteries and leads to the second stage, whereby the clinical features of the syndrome are featured. In this review, we summarize the modalities that have been studies so far to predict preeclampsia. The use of uterine artery Doppler and several other biomarkers such as vitamin D, soluble fms-like tyrosine kinase 1/placental growth factor (sFLT1/PlGF) ratio, soluble endoglin, and a subset of T-lymphocytes has shown promising results. We are still at early stages in this advance, and no clear recommendations have been made about their clinical use to date. Further studies are still needed to improve screening strategies and evaluate the cost-effectiveness of any intervention.

简介：AbstractPreeclampsia (PE), a multisystem disorder in pregnancy, is a main cause of perinatal mortality and is associated with long-term maternal complications. For a long time, PE was defined as the new onset hypertension and proteinuria after 20 weeks’ gestation. It had been shown that this "gold standard definition" is not able to provide a sufficient prediction of PE-related fetal and/or maternal complications. In 2018 the International Society for the Study of Hypertension in Pregnancy recommended a broader definition of the disease. The new definition of the International Society for the Study of Hypertension in Pregnancy ruled out proteinuria as mandatory for the diagnosis of PE. This new definition increases the number of patients diagnosed as preeclamptic by nearly 21%, which is not accompanied by an increased severity of maternal outcomes. Including angiogenic biomarkers, however, has been shown to increase detection of adverse outcomes.The pathophysiology of PE is complex and not yet completely explained. Advances in prediction and diagnosis have been achieved by discovery and clinical evaluation of biomarkers, especially of placental origin. A broad spectrum of biomarkers has been tested, a few of them have been introduced into the clinical practice as of today. Especially angiogenic biomarkers that are rooted in the pathophysiology of PE have been demonstrated to be important in the prediction and diagnosis of adverse outcomes. At a cut-off value of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF)-ratio of 85, early-onset PE <34+0 weeks of gestation can accurately be diagnosed with a sensitivity of 89% and a specificity of 97%. The Prediction of short-term outcome in pregnant women with suspected preeclampsia (PROGNOSIS) study has shown that the high negative predictive value (99.3%) of the sFlt-1/PlGF-ratio below 38 in patients with suspected PE rules out the onset of the disease within one week. PROGNOSIS Asia, evaluating the sFlt-1/PlGF-ratio cut-off of 38 in an Asian population, confirmed the excellent accuracy in prediction.Recently, the angiogenic biomarkers have been integrated in multi-marker prediction models. Digital approaches, integrating algorithm-based decision support tools paired with home monitoring devices may be the next step in enhancing predictive accuracy and thus bear the potential to reduce maternal and/or fetal morbidity and mortality and save costs for the payer in parallel. The objective of this review is to provide an overview of current methods for predicting and diagnosing PE.

简介：AbstractPreeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. This disorder has profound short-term and long-term impacts on both the affected woman’s and her child’s health. Early-onset PE requiring preterm delivery (preterm PE) is of particular importance because it is associated with a higher risk of adverse pregnancy outcomes than term PE. First trimester screening model developed by the Fetal Medicine Foundation (FMF), which uses Bayes-theorem to combine maternal characteristics and medical history together with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor, has been proven to be effective and have superior screening performance to that of traditional risk factor-based approach for the prediction of PE. Identification of high risk pregnant women for preterm PE and giving aspirin prophylaxis before 16th week of gestation would reduce the incidence of preterm PE. In Asia, although the prevalence of PE is slightly lower than the global estimation, early screening and prevention of this life-threatening condition is still crucial. The FMF Bayestheorem based screening method has been validated in a large-scale prospective Asia-wide study and revealed that the first trimester triple test achieves the highest detection rate, compared with the traditional risk factor-based approaches, and that the screening performance is comparable to the published data from the FMF in East Asian women. However, in order to achieve optimal screening performance, the key is to establish standardized methods for biomarker measurements and regular biomarker quality assessment, as each biomarker is susceptible to inaccurate measurement, thus affecting performance of screening. Furthermore, it is of great importance to emphasize that the optimal preventive effect of aspirin on preterm PE is clearly associated with good compliance to treatment. In conclusion, global implementation of an effective first trimester "screen and prevent" program for preterm PE would provide the opportunity to reduce the risk of both short-term maternal and perinatal morbidity and mortality, with the possibility of intergenerational prevention of future chronic diseases for both the mother and her offspring.

简介：AbstractThe syncytiotrophoblast, a fused single-cell layer between mother and fetus, constitutively releases extracellular vesicles (STBEV) directly into the maternal circulation. STBEV contain a variety of proteins and RNA which can be targeted to specific cells. In preeclampsia, asymptomatic placental oxidative stress is a precursor to later multi-organ dysfunction in the mother. Increased STBEV release in preeclampsia is considered a manifestation of syncytiotrophoblast stress, which may play a key role in signaling between fetus and mother. STBEV release in preeclampsia changes, both in terms of volume and content. In this review, we outline the latest advances in STBEV isolation and detection. We consider evidence for differential STBEV release, protein cargo and RNA content in preeclampsia, highlighting common pitfalls in study design. We summarise studies to date demonstrating STBEV actions on target cells. Ultimately, we consider how STBEV fit into the pathophysiology of the heterogeneous syndrome of preeclampsia. The key unifying concept in early- and late-onset preeclampsia is syncytiotrophoblast stress. We submit that STBEV are the key stress signal in preeclampsia. We believe that further investigation of STBEV release, content, and actions may offer valuable insights into preeclampsia pathophysiology and potential new clinical diagnostics and therapeutic targets.

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简介：AbstractPlacentation and tumorigenesis have many common features. Human placentation builds a maternal-fetal connection, circumvents maternal immune rejection of the fetus, and utilizes mechanisms that support tumorigenesis, such as proliferation, invasion, angiogenesis, and immune tolerance. Trophoblasts of the human placenta mimic the behavior of malignant cells, proliferating and invading the uterine decidua until reaching the myometrium and remodeling the spiral arteries that establish a new vascular system and escape the maternal immune response. These processes are under precise temporal and spatial regulation, and their dysregulation is associated with different pregnancy syndromes, including preeclampsia (PE), a pregnancy syndrome that is the leading cause of maternal and perinatal mortality and morbidity. At present, the precise mechanisms underlying the development of PE remain unclear. Here, we summarize and dissect the features between physiological placentation and pathological tumorigenesis to explore the pathogenesis of PE - which we believe to be the result of insufficient placentation, compared to the overaggression of tumorigenesis - to provide novel strategies to prevent and treat PE.

简介：AbstractNormal pregnancy is associated with dramatically increased estrogen biosynthesis whose role is believed to raise uterine blood flow to facilitate the bi-directional maternal-fetal exchanges of gases (O2 and CO2), to deliver nutrients, and exhaust wastes to support fetal development and survival. Constrained uterine blood flow in pregnancy is a leading cause of preeclampsia with fetal growth restriction, rendering investigations of uterine hemodynamics to hold a high promise to inform pathways as targets for therapeutic interventions for preeclampsia. The mechanisms of estrogen-induced uterine vasodilation in pregnancy have long been attributed to enhanced endothelium production of nitric oxide, but clinical trials targeting this pathway that dominates uterine hemodynamics have achieved no to little success. Emerging evidence has recently shown a novel proangiogenic vasodilatory role of hydrogen sulfide in regulating uterine hemodynamics in pregnancy and preeclampsia, provoking a new field of perinatal research in searching for alternative pathways for pregnancy disorders especially preeclampsia and intrauterine growth restriction. This minireview is intended to summarize the nitric oxide pathway and to discuss the emerging hydrogen sulfide pathway in modulating estrogen-induced uterine vasodilation in pregnancy and preeclampsia.

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简介：AbstractBackground:Preeclampsia (PE) is a serious complication that affects maternal and perinatal outcomes. However, the mechanisms have not been fully explained. This study was designed to analyze longitudinal gut microbiota alterations in pregnant women with and without PE in the second (T2) and third trimesters (T3).Methods:In this nested case-control study, which was conducted at Nanjing Maternity and Child Health Care Hospital, fecal samples from 25 PE patients (25 fecal samples obtained in T2 and 15 fecal samples obtained in T3) and 25 matched healthy controls (25 fecal samples obtained in T2 and 22 fecal samples obtained in T3) were collected, and the microbiota were analyzed using 16S rRNA gene sequencing. The diversity and composition of the microbiota of PE cases and controls were compared.Results:No significant differences in diversity were found between the PE and control groups (P > 0.05). In the control group, from T2 to T3, the relative abundances of Proteobacteria (median [Q1, Q3]: 2.25% [1.24%, 3.30%] vs. 0.64% [0.20%, 1.20%], Z = -3.880, P < 0.05), and Tenericutes (median [Q1, Q3]: 0.12% [0.03%, 3.10%] vs. 0.03% [0.02%, 0.17%], Z= -2.369, P < 0.05) decreased significantly. In the PE group, the relative abundance of Bacteroidetes in T2 was lower than in T3 (median [Q1, Q3]: 18.16% [12.99%, 30.46%] vs. 31.09% [19.89%, 46.06%], Z= -2.417, P < 0.05). In T2, the relative abundances of mircrobiota showed no significant differences between the PE group and the control group. However, in T3, the relative abundance of Firmicutes was significantly lower in the PE group than in the control group (mean ± standard deviation: 60.62% ± 15.17% vs. 75.57% ± 11.53%, t= -3.405, P < 0.05). The relative abundances of Bacteroidetes, Proteobacteria, and Enterobacteriaceae were significantly higher in the PE group than in the control group (median [Q1, Q3]: 31.09% [19.89%, 46.06%] vs. 18.24% [12.90%, 32.04%], Z=-2.537, P < 0.05; 1.52% [1.05%, 2.61%] vs. 0.64% [0.20%, 1.20%], Z=-3.310, P < 0.05; 0.75% [0.20%, 1.00%] vs. 0.01% [0.004%, 0.023%], Z = -4.152, P < 0.05). Linear discriminant analysis combined effect size measurements analysis showed that the relative abundances of the phylum Bacteroidetes, class Bacteroidia and order Bacteroidales were increased in the PE group, while those of the phylum Firmicutes, the class Clostridia, the order Clostridiales, and the genus unidentified Lachnospiraceae were decreased in the PE group; and these differences were identified as taxonomic biomarkers of PE in T3.Conclusion:From T2 to T3, there was an obvious alteration in the gut microbiota. The gut microbiota of PE patients in T3 was significantly different from that of the control group.

简介：AbstractObjective:To determine the incidence of preeclampsia (PE) and preterm PE in Spain and to identify the risk factors for developing the disease.Methods:This is a multicenter prospective cohort study performed at six maternity units across Spain. Women with singleton pregnancies attending their first-trimester routine visit at the hospital were offered participation. Maternal and pregnancy characteristics, including mean arterial pressure, as well as ultrasound findings were recorded. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for subsequent development of PE.Results:A total of 5868 pregnancies were recruited for this study, including 174 (3.0%) cases of PE, 47 (0.8%) cases of preterm PE and 127 (2.2%) cases of term PE. Median maternal age was 33.9 years (interquartile range: 30.1 to 36.9) and median gestational age at the routine visit was 12.7 weeks (interquartile range: 12.3 to 13.0). However, 293 (5.0%) of the women were on aspirin treatment during pregnancy, likely reducing the true incidence of the disease. As expected, increasing body mass index (P < 0.001), uterine artery pulsatility index (P= 0.011) and mean arterial pressure (P < 0.001), assisted conception (P= 0.013), previous personal (P < 0.001) or family history of PE (P= 0.024) and chronic hypertension (P= 0.001) were identified as independent risk factors for developing subsequent PE during pregnancy. Screening for PE by maternal factors alone leads to a detection rate of 36.8% (64/174) at 10.0% (587/5868) screen positive rate.Conclusion:In Spain, 3.0% of singleton pregnancies are complicated by PE and 0.8% require delivery before term due to its severity. Screening of PE by risk factors alone is only able to detect about 40% of total PE at 10% screen-positive rate.

简介：AbstractObjective:The aims of this study were to determine the differences between women with single vs. recurrent episodes of preeclampsia in term of: (1) the outcome of the first pregnancy affected by preeclampsia; and (2) the perinatal outcomes of subsequent pregnancies.Methods:This population based retrospective cohort study included all multiparous patients with a singleton gestation who delivered at Soroka University Medical Center (Beer Sheva, Israel) from January 1988 until December 2012, meeting the inclusion criteria, those who had fetuses with chromosomal or anatomical abnormalities were exclude. Our cohort included 213,558 deliveries that met the inclusion criteria, of them 208,017 had normotensive pregnancies and 5541 had preeclampsia. The latter group was further divided into those who had a single episode of preeclampsia followed by normotensive gestations (n=3879), and women who had recurrent preeclampsia (n=1662). We used parametric and non-parametric statistics as appropriate.Results:(1) Women with recurrent preeclampsia had an increased rate of early ((130/1662) 7.8% vs. (171/3879) 4.4%, P<0.001) and late ((268/1662) 16.1% vs. (438/3879) 11.3%, P<0.001) preterm deliveries than a single episode of preeclampsia; (2) of interest, the rate of chronic hypertension is higher in the first pregnancy of those with a single preeclampsia episode (P<0.001), while women with recurrent preeclampsia developed it in the subsequent gestations (P<0.001); (3) the rate of small for gestational age neonates in the index pregnancy was higher in those with recurrent rather than a single episode of preeclampsia (single episode 450/3879,11.6%, recurrent preeclampsia 244/1662, 14.7%, P=0.002); (4) patients with recurrent disease had an increased rate of cesarean deliveries in the subsequent pregnancies (P<0.001); and (5) patients who developed severe preeclampsia in the subsequent gestations had lower mean birthweight (P<0.001), a higher rate of perinatal mortality (P<0.001), and a lower Apgar score at 1 and 5 minutes (P<0.001), than those who developed mild preeclampsia in subsequent pregnancies, those with a single episode of preeclampsia and the control group.Conclusion:Recurrent preeclampsia increases the rate of pregnancy complications in the following gestations. Early onset preeclampsia at the index pregnancy of women with recurrent preeclampsia, is associated with increased risk for severe preeclampsia, placental abruption and perinatal mortality in subsequent pregnancies.

简介：AbstractObjective:This study aimed to evaluate the incidence and associated clinical risk factors for preeclampsia (PE) and its subtypes in a large multicentre retrospective study of Beijing, China.Methods:This study was conducted as a secondary analysis from the Gestational diabetes mellitus Prevalence Survey (GPS), a multicentre retrospective cohort study, which included 15 hospitals in Beijing, China. This analysis included 15,003 pregnant women who delivered in Beijing from June 20th to November 30th, 2013. The incidence of PE was calculated. Risk factors for PE, including maternal age, pre-gestational body mass index (BMI), parity, chronic hypertension, pre-existing diabetes, and gestational diabetes mellitus, were assessed. PE was defined as early- or late-onset PE based on clinical manifestations during the week of delivery, and mild or severe PE based on the severity of the disease. Logistic regression analysis was used to quantify the association with the risk factors, and data were displayed as odds risks (OR) and 95% confidence interval (CI).Results:The overall incidence of PE was 2.65% (397/15,003). The prevalence of early-onset and late-onset PE was 0.36% (54/15,003) and 2.29% (343/15,003), respectively. The prevalence of mild and severe PE was 0.91% (137/15,003) and 1.73% (260/15,003), respectively. Risk factors including high BMI considered overweight (adjusted odds risk (aOR): 1.48; 95% CI: 1.06-2.05; P= 0.02) and obesity (aOR: 2.15; 95% CI: 1.50-3.08; P < 0.001), nulliparity (aOR: 1.73; 95% CI: 1.32-2.25; P < 0.001), multiple gestation (aOR: 4.58; 95% CI: 2.86-7.32; P < 0.001), and chronic hypertension (aOR: 34.95; 95% CI: 26.60-45.93; P < 0.001), were associated with increased risk for PE. Only chronic hypertension (aOR: 13.75; 95% CI: 4.78-39.58; P < 0.001) was a significant risk factors for early-onset PE, whereas high BMI considered both overweight (aOR: 1.54; 95% CI: 1.09-2.18; P= 0.01) and obesity (aOR: 2.23; 95% CI: 1.53-3.27; P < 0.001), nulliparity (aOR: 2.00; 95% CI: 1.49-2.68; P < 0.001), multiple gestation (aOR: 4.11; 95% CI: 2.40-7.05; P < 0.001), and chronic hypertension (aOR: 35.57; 95% CI: 26.66-47.47; P < 0.001) were more relevant risk factors for late-onset PE. Risk factors including obesity (aOR: 2.20; 95% CI: 1.28-3.76; P < 0.01 and aOR: 1.80; 95% CI: 1.16-2.80; P= 0.01), nulliparity (aOR: 2.28; 95% CI: 1.44-3.60; P < 0.001 and aOR: 1.48; 95% CI: 1.09-2.02; P= 0.01), multiple gestation (aOR: 5.50; 95% CI: 2.87-10.67; P < 0.001 and aOR: 3.51; 95% CI: 1.93-6.41; P < 0.001), and chronic hypertension (aOR: 33.98; 95% CI: 22.20-52.01; P < 0.001 and aOR: 35.03; 95% CI: 25.40-48.31; P < 0.001) were associated with mild and severe PE. Moreover, we found that women with an increasing number of these risk factors had a higher risk of developing PE than pregnant women without any identified risk factors.Conclusion:The incidence of PE in this study is consistent with previous reported studies. Our findings indicate chronic hypertension and multiple gestation are the most important risk factors for PE in Chinese pregnant women. The risk for developing PE is associated with both the type and abundance of risk factors. These factors are valuable when monitoring patients at risk for PE, as this can help ensure an earlier diagnosis and prediction in women who are more likely to develop PE.

简介：AbstractObjective:The objective of this study was to investigate the expression levels of microRNA-141-5p(miRNA-141-5p), MAPK1 and neutrophil elastase in patients with and without preeclampsia (PE), and the relationship between miRNA-141-5p and MAPK1 with respect to the secretion of elastase by neutrophils in patients with PE.Methods:Thirty patients with PE and 30 healthy pregnant (HP) women were recruited from The Second Hospital of Shanxi Medical University, Taiyuan, China, between February 2017 and July 2018. Neutrophils were isolated from 8 mL peripheral blood samples and cultured. We recorded neutrophil count and morphology during culture. Apoptosis was detected by flow cytometry in different groups at 0, 24, and 48 h. The expression levels of elastase were detected in neutrophils by enzyme-linked immunosorbent assay, whereas the expression levels of miRNA-141-5p in peripheral blood neutrophils were detected by real-time polymerase chain reaction. We used TargetScanHuman Release 7.2 to analyze the target genes of miRNA-141-5p. The expression of MAPK1 in peripheral blood neutrophils was detected by western blotting. Data were analyzed by SPSS version 21.0 software, and comparisons between groups were carried out with the Student t test.Results:There was no significant difference between the PE and HP groups (P > 0.050) with regard to age or body mass index. The weight of newborns in the PE group (2846.00 ± 600.00 g) was significantly lower than that in the HP group (3055.00 ± 230.68 g). The number of neutrophilic granulocytes(NGs) in blood samples from the PE group was significantly higher than that in the HP group (P = 0.003). There was no significant difference between the groups with regard to morphology. Apoptosis in the PE group was delayed when compared with the HP group at different time points. The P value of apoptosis in the PE and HP groups were respectively 0.790, < 0.001 and 0.030 at 0 h, 24 h and 48 h. The expression levels of miRNA-141-5p in the PE group were significantly lower than those in the HP group (P < 0.050). The expression levels of MAPK1 in neutrophils from the PE group were significantly higher than those in the HP group (P < 0.050) by western blot. The expression levels of elastase in neutrophils from the PE group were significantly higher than those in the HP group (P < 0.050). Furthermore, the number of NGs in peripheral blood from the PE group was higher than that of the HP group; however, the levels of apoptosis were lower. The expression levels of miRNA-141-5p in NGs decreased, the expression of MAPK1 increased, and the secretion of neutrophil elastase in the NG medium increased in the PE group than those in the HP group.Conclusion:Collectively, our analysis suggested that miRNA-141-5p may be involved in the pathogenesis of PE by regulating the MAPK1 signaling pathway to activate neutrophils and increase the secretion of elastase.

简介：AbstractPreeclampsia remains associated with an increased risk of maternal and perinatal morbidity and mortality, and the burden of that excess risk is largely borne by pregnant women and their families in low- and middle-income countries (LMICs). Therefore, the Bill & Melinda Gates Foundation funded the PREeclampsia - Eclampsia Monitoring, Prevention, and Treatment (PRE-EMPT) initiative to accelerate progress. From PRE-EMPT, and related activity, have come a number of impactful findings. First, there is increasing global support for broadening the definition of preeclampsia to include women with hypertension and either significant proteinuria or evidence of target organ damage or fetoplacental compromise (including evidence angiogenic imbalance). Second, using blood pressure (BP) data from the Community-Level Interventions for Preeclampsia trials in India, Mozambique, and Pakistan, acquired on validated-for-pregnancy, semi-automated, low-cost BP devices, there are now population-level, rather than facility-based, estimates for the burden of pregnancy hypertension (sub-categorized into preeclampsia (4%-6%), gestational hypertension (7%-12%), and chronic hypertension (0.3%-0.6%)). Third, there is an identified need to understand biological pathways that underlie the causation of preeclampsia in LMICs. Fourth, the Community-Level Interventions for Preeclampsia trials have shown that providing at least eight antenatal contacts, in this case using digital health-supported community health workers, cost-effectively reduces the burden of maternal (by 60%), fetal (60%), and neonatal (40%) mortality. Fifth, what is the utility and cost-effectiveness of routine proteinuria screening of normotensive pregnant women? Sixth, clinical risk factor-based prediction of preeclampsia remains most relevant for most women in LMICs; calcium replacement (≥1 g/day) and low-dose aspirin (100-175 mg/day) are the most useful directly preventative interventions. However, achieving sustainable development goals (SDGs) not directly related to health are more likely to reduce the global burden of preeclampsia and its consequences. Seventh, should a woman develop preeclampsia, personalized maternal time-of-disease risk estimates are available through the PIERS (Preeclampsia Integrated Estimate of RiSk) models, either with (fullPIERS) or without (miniPIERS) access to laboratory testing. Assessment of perinatal risks in LMICs is largely driven by gestational age; however, evidence of significant angiogenic imbalance may identify risk of intrauterine fetal death. Eighth, Control of Hypertension in Pregnancy Study trial data show that women with non-severe pregnancy hypertension (systolic BP 140-159 mmHg or diastolic BP (dBP) 90-109 mmHg) should receive an antihypertensive medication for a target dBP of 85 mmHg. Ninth, for women with severe pregnancy hypertension (systolic BP ≥160 mmHg or dBP ≥110 mmHg), oral antihypertensive management with either nifedipine, labetalol, or, less so, methyldopa will lower BP into the non-severe hypertension range. Tenth, magnesium sulfate remains the sole agent of choice for preventing and treating eclamptic seizures. Eleventh, corticosteroids should be administered to women at risk of delivery <35+0 weeks’ gestation. Twelfth, although delivery of the placenta initiates resolution of the maternal syndrome of preeclampsia, decisions to initiate delivery should be guided by gestational age and maternal and fetal status. Many women will experience significant postpartum deterioration; delivery should not be equated with "cure" . Thirteenth, whether the development of preeclampsia identifies women at increased risk for early-onset cardiovascular disease in LMICs must be determined.

简介：AbstractObjective:The role of Vitamin D-binding protein (DBP) in preeclampsia (PE) pathogenesis is unknown. In this study, we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls, and aimed to explore the effect of DBP on endothelial cells (ECs) and the underlying mechanism.Methods:DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry. The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA (siRNA) and DBP-expression vector, respectively. The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC (HUVEC) cultures. Angiogenic effects on HUVECs were assessed by tube formation assays, and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer. The expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-2, as well as the phosphorylation of different residues of VEGFR-2 in HUVECs, were determined by western blotting.Results:DBP expression was significantly increased in the placental tissues collected from PE patients. The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs, in addition to their proliferation and migration. Furthermore, treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996, whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951, 996, and 1,175.Conclusions:The expression of DBP is increased in the placentas of PE patients. DBP plays potential roles in endothelial dysfunction, which contributes to PE development, by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.

简介：AbstractObjective:This study was aimed to determine the changes in CXCR2 expression in preeclampsia placenta and its correlation with clinical parameters.Methods:Sixty-four gravidas ranging in age from 25 to 42 years referred to the obstetrics unit of the West China Second University Hospital from April 2012 to October 2012 were recruited in this case-control study; women were diagnosed and divided into early-onset preeclampsia group (n= 22), late-onset preeclampsia group (n= 22), and healthy pregnancy group (n= 20). After immunolocalized in human placenta, the levels of CXCR2 protein and messenger ribonucleic acid (mRNA) were detected by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Correlations between placental CXCR2 protein expression with systolic blood pressure and lactate dehydrogenase (LDH) in early-onset preeclampsia were examined using Pearson or Spearman’s correlation coefficients.Results:Placental CXCR2 protein and mRNA expression in early-onset preeclampsia was significantly lower than it was in placentas from healthy pregnancy pregnancies and late-onset preeclampsia (P < 0.05). The placental CXCR2 protein expression correlated negatively with systolic blood pressure and LDH in early-onset preeclampsia (r= -0.51, P < 0.05; r=-0.43, P < 0.05).Conclusion:Significant abnormal placental CXCR2 expression in early-onset preeclampsia, and its correlations with some clinical parameters (systolic blood pressure and LDH) were discovered, suggesting that CXCR2 may play a role in the pathogenesis of early-onset preeclampsia.