Pre-eclampsia Concentrations Research Articles

Plasma eNOS Concentration in Healthy Pregnancy and in Hypertensive Disorders of Pregnancy: Evidence of Reduced Concentrations in Pre-Eclampsia from Two Independent Studies.

Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS). However, no previous study has investigated plasma eNOS concentrations in patients with GH and PE. In this study, we compared plasma eNOS concentrations in healthy pregnancies and HDP in two independent cohorts. The primary study included 417 subjects, with 43 non-pregnant (NP) and 156 healthy pregnant (HP) women and 122 patients with GH and 96 with PE. The replication study included 85 pregnant women (41 healthy and 44 pre-eclamptic). Plasma concentrations of eNOS were measured using a commercial ELISA kit provided by R&D Systems, and plasma nitrite concentrations were assessed using two ozone-based chemiluminescence assays. Correlations between plasma eNOS concentrations and plasma nitrite concentrations, as well as clinical and biochemical parameters, were evaluated by either Spearman's or Pearson's tests. In the primary study, NP women and HDP had significantly lower plasma eNOS concentrations compared to HP; concentrations were even lower in PE compared to GH. Plasma eNOS concentrations were reduced but not significant in early-onset PE, PE with severe features, preterm birth, and intrauterine growth restriction. No correlation was observed between plasma eNOS and nitrite levels. In HDP, there was a significant positive correlation between levels of eNOS and hemoglobin (r = 0.1496, p = 0.0336) as well as newborn weight (r = 0.1487, p = 0.0316). Conversely, a negative correlation between eNOS levels and proteinuria was observed (r = -0.2167, p = 0.0179). The replication study confirmed significantly reduced plasma concentrations of eNOS in PE compared to HP. Our findings provide evidence of reduced plasma eNOS concentrations in HDP; they were particularly lower in PE compared to GH and HP in two independent studies.

What is in common between preeclampsia, HPS70 and medieval headwear? Part I. Serum HPS70 in preeclampsia: systematic review and meta-analysis

The objective: to investigate the relationship between HSP70 concentrations in maternal serum and preeclampsia and assess the prospects of using HSP70 as a preeclampsia predictor.Materials and methods. The original publications, which study HSP70 in maternal serum of preeclamptic women, were searched and analyzed. Papers were identified with Scopus, PubMed Central, Virtual Health Library databases, published before January 2023, the keywords were «HSP70», «preeclampsia», «heat shock protein 70», «pregnant». Statistical analysis was performed via software EZR 1.55.Results. 16 case-control studies were included, making a total of 751 pregnant women with preeclampsia and 719 healthy pregnant women. The analysis found the statistically significant difference between HSP70 concentrations in maternal serum of preeclamptic and healthy pregnant patients. Cochrane Q-test showed high heterogeneity among studies (p<0.01), the value of the І2 statistic was 97%. Dividing the studies into groups made it possible to reduce or remove heterogeneity completely. This high level of heterogeneity for publications together, but low within most groups, suggests that there are certain factors that significantly influence some studies.Conclusions. The conducted systematic review and meta-analysis confidently indicate an increased average serum concentration of HSP70 in pregnant women with preeclampsia compared to healthy pregnant women at the corresponding gestational age.No statistically significant relationship was found between increased HSP70 concentration in preeclampsia and pregnant women’s age, gestational age, systolic and diastolic blood pressure. Quantitative assessment of HSP70 levels is complicated by the lack of a single standard for laboratory diagnostics. The case-control design of the presented studies limits their significance.The use of HSP70 as a predictor of preeclampsia is promising, but requires further study and prospective cohort studies.

Association of Hypertensive Disorders of Pregnancy with variations in Serum Sodium and Potassium Concentration

Objective: To study the variation in Serum Sodium and Potassium concentration in Pre-eclampsia and Normotensive pregnant ladies.
 Study Design: Cross-sectional study.
 Place and Duration of the Study: Combined Military Hospital, Kharian District Gujrat Pakistan, from Jun 2020 to Jan 2021.
 Methodology: The study population Comprosed of 80 pre-eclamptic and 80 normotensive pregnant women recruited consecutively at their first, third trimester, and prenatal visits. Serum Sodium and Potassium were analysed using Ericson Photometer.
 Results: When the two Groups were compared, in the Normotensive Group, the mean Sodium concentration of 132±4.490 mEq/dl was significantly less than the Pre-eclampsia Group of 139.1±3.909 mEq/dl. On the contrary, mean Serum Potassium concentration was significantly less in Pre-eclampsia 3.54±0.511 mmol/L compared to the Normotensive Group to 4.0±0.513 mmol/L.
 Conclusion: High levels of Sodium and low level of Potassium were observed in the Pre-eclampsia Group. There may be a causal relationship between electrolyte fluctuations and Pre-eclampsia.Keywords: Electrolytes, Hypertension, Potassium, Pre-eclampsia, Sodium.

D-Dimer Concentrations in Preeclampsia and Normal Pregnancy in Kinshasa

D-Dimer Concentrations in Preeclampsia and Normal Pregnancy in Kinshasa

Levels of serum podocalyxin in preeclampsia and relationship with maternal echocardiographic and Doppler ultrasound parameters.

Podocalyxin (PCX) is an indicator of glomerular injury. Aside from the kidney, it is expressed in the endothelial cells of various organs. Echographic examinations are useful in assessing the alterations in cardiovascular structure and function during pregnancy.

Circulating levels of tissue inhibitor of metalloproteinase 3, a protein with inhibitory effects on angiogenesis, are increased in pre-eclampsia.

To assess and compare circulating tissue inhibitor of metalloproteinase 3 (TIMP-3) concentrations between women with pre-eclampsia and healthy pregnant women. We also aimed to determine the relationships between circulating TIMP-3 and matrix metalloproteinase 2 (MMP-2), MMP-9, TIMP-1, and TIMP-2 concentrations in pre-eclampsia. A primary case-control study included patients with pre-eclampsia (n= 219) and gestational hypertension (n= 118), healthy pregnant women (n= 214), and non-pregnant women (n= 66), and a replication case-control study included patients with pre-eclampsia (n= 177) and healthy pregnant women (n= 124), all from southeastern Brazil. Plasma TIMP-3, MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations were assessed using commercially available enzyme-linked immunosorbent assay kits, and the relationships between them were analyzed using Spearman's correlation. In our primary study, patients with pre-eclampsia and gestational hypertension exhibited increased TIMP-3 concentrations compared with healthy pregnant women (both P< 0.0001) and non-pregnant women (both P< 0.001). These findings were confirmed in the replication study, showing elevated TIMP-3 concentrations in women with pre-eclampsia versus healthy pregnant women (P< 0.001). We found no difference in TIMP-3 concentrations between early-onset and late-onset pre-eclampsia. Moreover, TIMP-3 concentrations were significantly correlated with plasma concentrations of TIMP-1 (r= 0.2333; P= 0.0086) and MMP-2 (r= 0.2159; P= 0.0156) in pre-eclampsia. Circulating TIMP-3 concentration is increased in women with pre-eclampsia compared with healthy pregnant women, and it is positively correlated with plasma MMP-2 and TIMP-1 concentrations in pre-eclampsia.

Evaluation of the predictive values of elevated serum l-homoarginine and dimethylarginines in preeclampsia

l-homoarginine (hARG) is involved in nitric oxide biosynthesis, but its role and concentration in preeclampsia (PE) have not been fully revealed. The purpose of this study was to develop and validate a feasible clinical assay to quantify serum hARG, arginine (ARG), asymmetric (ADMA) and symmetric dimethylarginines (SDMA) levels by LC–MS/MS and investigate their differences at different stages of pregnancy with or without preeclampsia. Serum samples were collected from 84 pregnant women without complications (controls), 84 with mild preeclampsia (MPE), and 81 with severe preeclampsia (SPE) at various gestation stages (before the 20th week, during the 20th–28th week or after the 28th week of gestation). No significant difference in ARG levels was observed between PE and controls at any stage (P > 0.05). The serum hARG levels and hARG/ADMA ratios of MPE before the 20th week were higher than those of controls (P < 0.001). ADMA levels of MPE were higher than those of controls during the 20th–28th week (P < 0.01). SDMA levels of SPE were higher than those of MPE (P < 0.01) and controls (P < 0.05) after the 28th week. Elevated serum hARG before the 20th week was identified as an independent predictor for PE (OR = 1.478, 95% CI 1.120–1.950). ROC curve analysis showed serum hARG before the 20th week had a good potential to predict MPE (AUC = 0.875, 95% CI 0.759–0.948). In conclusion, our study indicated that elevated serum hARG and dimethylarginine levels detected by LC–MS/MS might serve as potential biomarkers for the early prediction of PE.

NAMPT Single-Nucleotide Polymorphism rs1319501 and Visfatin/NAMPT Affect Nitric Oxide Formation, sFlt-1 and Antihypertensive Therapy Response in Preeclampsia

Aim: We examined the relationships between visfatin/NAMPT and nitrite concentrations (a marker of nitric oxide [NO] formation) or sFlt-1 levels in 205 patients with preeclampsia (PE) responsive or nonresponsive to antihypertensive therapy, and whether NAMPT SNPs rs1319501 and rs3801266 affect nitrite concentrations in PE and 206 healthy pregnant women. Patients & methods: Circulating visfatin/NAMPT and sFlt-1 levels were measured by ELISA, and nitrite concentrations by using an ozone-based chemiluminescence assay. Results: In nonresponsive PE patients, visfatin/NAMPT levels were inversely related to nitrite concentrations and positively related to sFlt-1 levels. NAMPT SNP rs1319501 affected nitrite concentrations in nonresponsive PE patients and was tightly linked with NAMPT functional SNPs in Europeans. Conclusion:NAMPT SNP rs1319501 and visfatin/NAMPT affect NO formation, sFlt-1 levels and antihypertensive therapy response in PE.

Prognostic role of increased serum homocysteine concentration in preeclampsia

ABSTRACT Objective: To assess homocysteine (Hcy) concentration in women with preeclampsia (PE). Methods: Hcy concentrations were detected by ELISA in 305 pregnancies. Results: Hcy concentration in patients with PE was 16.07 umol/L at 10–14 weeks as compared to 7.19 umol/L in normotensive pregnancies (p < 0.0001). Optimal cutoff level for Hcy in the first trimester of pregnancy was >9.55 umol/L with area under curve of 0.859, sensitivity of 91.67%, specificity of 72.24%. Conclusion: Assessment of serum Hcy concentration may be used as a predictor of PE, with the highest diagnostic utility in the first trimester of pregnancy.

Maternal serum Apelin 13 and APLN gene promoter variant -1860T > C in preeclampsia

Objective To evaluate the apelin (APLN) −1860 T > C (rs56204867) polymorphism and maternal serum apelin 13 levels in preeclampsia and its association with blood pressure. Methods This case-control study was conducted in department of Biochemistry, Sri Devaraj Urs Medical College, Karnataka, India. A total of 181 subjects were enrolled in the study from department of Department of Obstetrics and Gynecology. The recruited women were grouped as: Group–I (n = 91) cases with preeclampsia and Group–II (n = 90) normotensive healthy pregnant women as controls. Under aseptic conditions, the collected 5 mL blood was distributed for serum separation (3 mL) and genetic analysis (2 mL). Serum was stored at −80 °C after centrifugation at 3000 rpm for 10 min. The collected five mL urine sample was used for urinary protein analysis by dipstick method. The APLN gene −1860 T > C polymorphism and Apelin 13 levels were analyzed by molecular methods and ELISA technique respectively. Birth weight and demographic details were recorded. Results In the present study, no significant difference was observed for mean gestational age and maternal age. Systolic (158.7 ± 14.0 mmHg) and diastolic (104.9 ± 10.7 mmHg) blood pressure, and mean arterial pressure (MAP) (123.0 ± 11.1 mmHg) (p-value .001) were significantly increased in preeclamptic women compared with healthy pregnant women. Birth weight (2.4 ± 0.5 kg) (p-value .001) was significantly decreased in babies born to preeclamptic mothers. Birth weights were also expressed in centiles, according to Fenton Chart. Number of small for gestational age (SGA) babies were more in preeclampsia (n = 55) than healthy pregnant women (n = 28). Mean maternal serum apelin 13 (239.4 ± 126.3 pg/mL) (p-value .001) concentrations were significantly lower in preeclampsia compared with healthy controls. Maternal serum apelin 13 concentration in preeclampsia was negatively correlated with systolic blood pressure (r = −0.235), diastolic blood pressure (r= −0.172) and mean arterial pressure (r = –0. 206). However, maternal serum apelin 13 levels showed insignificant positive correlation with age, gestational age and birth weight. The genotype and allele frequencies of APLN gene were found significant between study groups as in preeclampsia (χ2 = 11.69; df = 2; p = .0028 and χ2 = 14.27; df = 1; p = .00013 respectively). CC genotype and C allele of APLN − 1860 T > C site was high in preeclampsia. Conclusion Study concludes that preeclamptic women have low level of serum apelin 13 and −1860 T > C polymorphism at APLN gene promoter site with increased allelic frequency of CC genotype and C allele compared to normotensive pregnant women. And this evidence may link to cardiac complications in preeclamptic women after delivery in later stage.

Apelin 13 and Blood Pressure, Is there any Association in Pre-eclampsia? - A Case-control Study

Introduction: Pre-eclampsia is a pregnancy specific disorder, characterised by the onset of hypertension and proteinuria. Pre-eclampsia is the leading cause of maternal, perinatal morbidity and mortality. The exact cause of pre-eclampsia is not known clearly and needs to be explored. Aim: To evaluate the maternal serum apelin 13 levels among pre-eclampsia and healthy pregnant women and also, to find the association between apelin 13 and blood pressure. Materials and Methods: A case-control study was conducted between Department of Biochemistry and Department of Obstetrics and Gynaecology, RL Jalappa Hospital and Research Centre, Kolar, Karnataka, India. After approval from the Institutional Ethics Committee and written informed consent from study subjects, a total of 270 pregnant women were recruited for this study. Among them, 135 pre-eclamptic women were considered as cases and 135 normotensive healthy pregnant women served as controls. According to the pre-eclampsia severity, cases were grouped into mild (n=47) and severe pre-eclampsia (n=88). Blood samples were collected from all the study subjects and was analysed for apelin 13 by Enzyme Linked Immunosorbent Assay (ELISA) method. Maternal and foetal adverse outcomes were recorded. Results were expressed as mean±Standard Deviation (SD). Categorical variables were expressed in percentages. Spearman’s correlation was applied and p&lt;0.05 was considered significant. Results: The mean gestational age was 36.66±3.69 weeks which was, significantly low in pre-eclamptic women compared with healthy pregnant women. BMI (26.94±3.81 kg/m2), systolic (157.82±15.14 mmHg), diastolic (101.68±11.02 mmHg) and Mean Arterial Pressure (MAP) (120.20±11.12 mmHg), pulse rate (88.14±5.82 bpm), Aspartate Transaminase (AST) (25.25±12.49 IU/L) and Alanine Transaminase (ALT) (19.01±10.95 IU/L) were significantly increased in pre-eclamptic women when compared with control group. Mean maternal serum apelin 13 (341.44±218.63 pg/mL) concentrations were significantly lower in pre-eclampsia compared with healthy pregnant women. Maternal serum apelin 13 concentrations were negatively correlated with Systolic Blood Pressure (SBP) (r = -0.196), Diastolic Blood Pressure (DBP) (r = -0.172) and MAP (r =-0.204). Adverse maternal outcomes such as epigastric pain 75 (55.55%), oedema 62 (45.92%) and persistent headache 35 (25.92%) were higher in pre-eclamptic group. Additionally, adverse foetal outcomes were more in pre-eclamptic cases including significantly decreased birth weight (2.40±0.65), babies requiring Neonatal Intensive Care Unit (NICU) admission were 54 (40%), preterm birth (≤37 wks) in 50 (37.03%), Respiratory Distress Syndrome (RDS) 31 (22.96%), Small for Gestational Age (SGA) in 4 (2.96%) and Intra Uterine Death (IUD) in 11 (8.14%) babies. Conclusion: It was concluded from the present study that there was low maternal serum apelin 13 concentrations in pre-eclampsia and had negative correlation with blood pressure, suggesting its potential role in the pathophysiology of pre-eclampsia.

Evaluation of Nitric Oxide Concentrations in Preeclampsia and Normal Pregnancy

During pregnancy Nitric oxide is one of the most important relaxing factors for myometrium and also in the control of blood flow in uterus and placenta. Nitric oxide is generated by endothelial type II nitric oxide synthase (NOS) and acts as a vasodilator.&#x0D; Objective:To investigate the level of nitric oxide (NO) production in pregnancies complicated by preeclampsia and in normal pregnancy.&#x0D; Materials and Methods: A case control study was undertaken in Department of Gynaecology and Obstetrics of Bangabandhu Sheikh Mujib Medical University (BSMMU), from january to july 2014. The study population was pregnant women having preeclampsia and normal pregnancy who attended the OPD Department of Obstetrics and Gynecology in BSMMU between 29 to 40 weeks of gestation. As because of transient and volatile nature of nitric oxide, it was unsuitable to measure the nitric oxide level by conventional method. However, two stable break down product, nitrate (NO3 -) and nitrate (NO2 -) could be easily detected by sprectophototric means. Nitrate (NO2 -) was first converted to Nitrite (NO3 -) by reduction process using cadmium. Then concentration was measured by using Griess reagent in UV sprectophototric machine. This procedure was done in the Biochemistry Department, Dhaka University.&#x0D; Results: The mean nitrite level was found 18.37}3.64 mol/L in case group and 25.57}2.11mol/ L in control group, which was significantly (p&lt;0.05) higher in control group. The mean serum creatinine level was found 1.19}0.28 mg/dl in case group and 0.65}0.1 mg/dl in control group. The mean serum creatinine level was significantly (p&lt;0.05) higher in case groups. Nitrite level had no correlation with onset of hypertension (r=-0.006; p=0.966), onset of proteinuria (r=0.071; p=0.623), systolic blood pressure (r=0.012; p=0.933), diastolic blood pressure (r=-0.159; p=0.269) and urine protein (r=0.047, p=0.748).&#x0D; Conclusion: As pregnancy progressed there was a decrease in plasma nitric oxide levels in preeclampsia. Urine uric acid to creatinine ratio increased with the decrease in nitric oxide levels and can be used as a marker for preeclampsia.&#x0D; Bangladesh J Obstet Gynaecol, 2017; Vol. 32(2) : 60-66

Elevated cell-free fetal DNA contributes to placental inflammation and antiangiogenesis via AIM2 and IFI16 during pre-eclampsia.

Accumulated evidence has shown that pre-eclampsia (PE) is related to both maternal and utero-placental antiangiogenesis and inflammation. Remarkably, an elevated cell-free fetal DNA (cffDNA) level has been found in maternal circulation; however, it remains unclear whether this DNA can induce activation of cytosolic DNA sensor signaling pathways and lead to the development of PE. In this study, we found that trophoblast cells constitutively expressed the cytosolic DNA sensors, absent in melanoma 2 (AIM2) and interferon-inducible protein 16 (IFI16). The cffDNA and pro-inflammatory and antiangiogenic factors were present at higher concentrations in PE compared with the control group and correlated with the severity of PE. DNA stimulation significantly increased the AIM2 and IFI16 levels, consistent with the elevated AIM2 and IFI16 expression in women with PE, and elicited increased production of AIM2-mediatedinterleukin IL-8 (IL-8), IL-6 and CC chemokine ligand 2 (CCL2) and IFI16-mediated sEndoglin, sFlt-1 and CXCL10. Furthermore, enhancement of the inflammatory response was found to be induced by DNA exposure, but DNA exposure did not induce PE-like symptoms in pregnant mice. It is possible that elevated cffDNA could reflect the degree of placental damage and trigger cytosolic DNA sensoractivation, which disrupts the immunity balance and, consequently, contributes to inflammatory and antiangiogenic responses. In conclusion, the results of this study suggest that circulating cffDNA levels are increased in preeclamptic women and act through AIM2 and IFI16 activation to promote the production of pro-inflammatory and antiangiogenic factors, which correlate with the severity of the disease, and may offer insights into the etiology and pathogenesis of PE.

Early-onset preeclampsia, plasma microRNAs, and endothelial cell function

Preeclampsia is a hypertensive pregnancy disorder in which generalized systemic inflammation and maternal endothelial dysfunction are involved in the pathophysiology. MiRNAs are small noncoding RNAs responsible for post-transcriptional regulation of gene expression and involved in many physiological processes. They mainly downregulate translation of their target genes. We aimed to compare the plasma miRNA concentrations in preeclampsia, healthy pregnant women, and nonpregnant women. Furthermore, we aimed to evaluate the effect of 3 highly increased plasma miRNAs in preeclampsia on endothelial cell function invitro. We compared 3391 (precursor) miRNA concentrations in plasma samples from early-onset preeclamptic women, gestational age-matched healthy pregnant women, and nonpregnant women using miRNA 3.1. arrays (Affymetrix) and validated our findings by real-time quantitative polymerase chain reaction. Subsequently, endothelial cells (human umbilical vein endothelial cells) were transfected with microRNA mimics (we choose the 3 miRNAs with the greatest fold change and lowest false-discovery rate in preeclampsia vs healthy pregnancy). After transfection, functional assays were performed to evaluate whether overexpression of the microRNAs in endothelial cells affected endothelial cell function invitro. Functional assays were the wound-healing assay (which measures cell migration and proliferation), the proliferation assay, and the tube-formation assay (which assesses formation of endothelial cell tubes during the angiogenic process). To determine whether the miRNAs are able to decrease gene expression of certain genes, RNA was isolated from transfected endothelial cells and gene expression (by measuring RNA expression) was evaluated by gene expression microarray (Genechip Human Gene 2.1 ST arrays; Life Technologies). For the microarray, we used pooled samples, but the differently expressed genes in the microarray were validated by real-time quantitative polymerase chain reaction in individual samples. No significant differences (fold change <-1.2 or >1.2 with a false-discovery rate <0.05) were found in miRNA plasma concentrations between healthy pregnant and nonpregnant women. The plasma concentrations of 26 (precursor) miRNAs were different between preeclampsia and healthy pregnancy. The 3 miRNAs that were increased with the greatest fold change and lowest false-discovery rate in preeclampsia vs healthy pregnancy were miR-574-5p, miR-1972, and miR-4793-3p. Transfection of endothelial cells with these miRNAs in showed that miR-574-5p decreased (P<.05) the wound-healing capacity (ie, decreased endothelial cell migration and/or proliferation) and tended (P<.1) to decrease proliferation, miR-1972 decreased tube formation (P<.05), and also tended (P<.1) to decrease proliferation, and miR-4793-3p tended (P<.1) to decrease both the wound-healing capacity and tube formation invitro. Gene expression analysis of transfected endothelial cells revealed that miR-574-5p tended (P<.1) to decrease the expression of the proliferation marker MKI67. We conclude that in the early-onset preeclampsia group in our study different concentrations of plasma miRNAs are present as compared with healthy pregnancy. Our results suggest that miR-574-5p and miR-1972 decrease the proliferation (probably via decreasing MKI67) and/or migration as well as the tube-formation capacity of endothelial cells. Therefore, these miRNAs may be antiangiogenic factors affecting endothelial cells in preeclampsia.

Elevated soluble-St2 concentrations in preeclampsia correlate with echocardiographic parameters of diastolic dysfunction and return to normal values one year after delivery

Objectives: To compare soluble-ST2 (sST2) concentrations in patients with severe features of preeclampsia and healthy pregnant controls before as well as 1 year after delivery. Another objective was to assess potential correlation between sST2 concentrations and myocardial function.Methods: Patients with singleton pregnancy complicated by severe features of preeclampsia and healthy controls were included in a prospective observational study. Plasma sST2 concentrations were measured within 24 h before delivery and 1 year after delivery. Standard two-dimensional and Doppler echocardiography was performed at the time of first sST2 measurement before delivery. Mann–Whitney U test was used to compare sST2 values in preeclamptic patients versus controls. Kendall’s tau was used to assess correlation between sST2 values and echocardiographic measures of left ventricular systolic and diastolic function (p < .05 significant).Results: We included 24 patients with severe preeclampsia and 29 controls. One year after delivery, sST2 concentrations were available for 24 (45%) participants (13 in preeclampsia group and 11 controls). Concentrations of sST2 were markedly elevated in patients with severe preeclampsia compared to healthy controls before delivery (p = .04), but not 1 year after delivery (p = .80). There was no significant correlation between sST2 and parameters of systolic function. In preeclamptic patients, we found a significant inverse correlation between sST2 and markers of diastolic function: peak early mitral inflow velocity E (Kendall’s tau = −0.40; p = .02), peak early diastolic myocardial velocities at septal and lateral mitral annulus (e’) (Kendall’s tau = −0.354, p = .04) and ratio between e’ and peak systolic myocardial velocities at the septal and lateral mitral annulus (e'/s') (Kendall’s tau = −0.362, p = .04).Conclusions: Preeclampsia with severe features is associated with increased maternal plasma concentrations of sST2, which return to normal values in the first year after delivery. Higher sST2 levels in preeclamptic patients correlate with impaired parameters of left ventricular diastolic function.

Angiogenic profile and smoking in the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort

Objectives: The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke.Subjects and methods: First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women.Results: PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6–48.5) pg/ml, p = .001] and reduced sEng concentration [5.0 (4.6–5.6) ng/ml, p = .047] compared to PE non-smokers [30.0 (28.1–32.1) pg/ml and 6.1 (5.9–6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy.Conclusions: The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker.Key messagesSmoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies.Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker.

Comparison of Transforming Growth Factor-Beta 1 Concentration in Preeclampsia and Normal Pregnancy Women

BACKGROUND: According to the theory of endothelial dysfunction, the pathogenesis of preeclampsia is associated with the imbalance of angiogenic and anti-angiogenic factors. Transforming growth factor-beta 1 (TGF-β1) has also proposed as a proangiogenic factor that influences preeclampsia. This study was conducted to compare a mean difference of TGF-β1 between preeclampsia and normal pregnancy.METHODS: This study was an observational crosssectional study with 25 subjects of pregnant women with preeclampsia and 25 subjects of normotensive pregnant women. The study was conducted in Dr. Reksodiwiryo Hospital, Bhayangkara Hospital, and Dr. Rasidin Hospital in Padang, Indonesia from October 2015 to January 2016. For the determination of TGF-β1 concentration, peripheral Abstract venous blood samples were taken. The blood samples wereanalyzed by enzyme-linked immunosorbent assay (ELISA) in Biomedical Laboratory, Faculty of Medicine, Andalas University. The mean difference was statically analyzed by independent samples T-test.RESULTS: The mean difference of TGF-β1 was lower in preeclampsia group than normal pregnancy group (2.02±0.99 ng/mL vs. 3.24±2.67 ng/mL; p&lt;0.05).CONCLUSION: The TGF-β1 concentration was lower in pregnant women with preeclampsia. Thus, it may have a role as a marker in preeclampsia.KEYWORDS: preeclampsia, normal pregnancy, transforming growth factor-beta1, TGF-β1

Alteration of serum adropin level in preeclampsia.

To clarify the alterations in serum adropin and preptin concentrations in preeclampsia, we determined serum adropin and preptin levels in 29 women with normal pregnancy and 32 women with preeclampsia. We found that maternal age, body mass index and fetal gender were not significantly different between two groups; however, blood pressure, gestational age and neonatal birth weight were significantly different. Serum adropin levels were significantly increased in women with preeclampsia compared with those with normal pregnancy but there were no significant differences in preptin levels. An increase in maternal serum adropin level was found in preeclampsia, and this may be a compensation for pregnancy complicated with preeclampsia.

The effect of healthy pregnant plasma and preeclamptic plasma on the phagocytosis index of neutrophil granulocytes and monocytes of nonpregnant women

ABSTRACTObjective: Phagocyte function of neutrophil granulocytes and monocytes is decreased in healthy pregnancy and further decreased in preeclampsia. The cause of the declined function is unknown. Decreased phagocyte function can lead to the higher infection rate in healthy pregnancy and may also be responsible for the increased susceptibility to infections and high trophoblast concentration in preeclampsia. The aim of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes. Methods: Monocytes and neutrophil granulocytes were separated from the peripheral circulation of six nonpregnant patients and incubated in plasma samples from six healthy pregnant, six preeclamptic pregnant, and six nonpregnant patients. The cells were marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosan molecules. Results: Phagocyte function of neutrophils as well as monocytes from nonpregnant patients were decreased significantly when the cells were incubated in plasma samples from healthy pregnant patients, and further decreased when incubated in plasma samples from preeclamptic pregnant women. Conclusion: The decreased phagocyte function of neutrophil granulocytes and that of monocytes in healthy pregnancy and the further decreased phagocyte function in preeclampsia is caused by factor(s) in the maternal circulation.

Acute and Chronic Biological Effects of Copeptin on Vascular Function in Mice and Humans

BackgroundCopeptin, the 39 amino acid C‐terminal segment of the precursor protein of arginine vasopressin (AVP), is secreted from the posterior pituitary in a 1:1 ratio with AVP in response to osmotic and hemodynamic stimuli. Copeptin is significantly elevated in pregnant women with preeclampsia, and predicts the development of preeclampsia as early as the 6th week of gestation. Preliminary data in a recent prospective study demonstrated that higher copeptin was associated with lower endothelial function (brachial artery flow‐mediated dilation, FMD) during the 2nd trimester in pregnant women at high risk of preeclampsia. However, whether copeptin itself has any independent biological effects on the vasculature is completely unknown.Methods and ResultsChronic incubation of mouse aortic rings with copeptin (n=4 male mice, 1nM, 24 hours) had no effect on endothelium‐ dependent (acetylcholine) or ‐independent (sodium nitroprusside) vasodilatory responses, indicating the lack of effect on endothelial or vascular smooth muscle function. Similarly, circulating copeptin was not associated with brachial artery FMD in non‐pregnant young women (n=11, r= −0.08, P=0.81), postmenopausal women (n=15, r=0.06, P=0.82) or men (n=24, r=0.10, P=0.62). In contrast, acute incubation of aortic rings (n=6 male mice) with copeptin demonstrated a dose response vasodilation beginning at 1nM up to a maximum relaxation at 100nM (43.6 ± 15.5%, p&lt;0.05, n=6). Co‐incubation with the nitric oxide (NO) inhibitor of L‐NG‐Nitroarginine methyl ester (L‐NAME) significantly attenuated the max vasodilatory response to 12.5 ± 0.6%, indicating that the acute vascular response to copeptin is largely NO‐mediated. Incubation of aorta with copeptin (60 min, 0.5nM) caused a significant increase in protein kinase B (AktSer473) phosphorylation (Western blot) vs. control tissue (0.63 ± 0.19 vs 1.27 ± 0.6, p&lt;0.04, n=5) and a trend towards increased phosphorylation of eNOSSer1177 (0.69 ± 0.02 vs 0.91 ± 0.21, p&lt;0.3, n=2).ConclusionsThese data indicate that acute exposure of aorta of mice to high copeptin results in marked NO‐mediated vasodilation. However, chronic exposure to high copeptin does not alter vascular endothelial or smooth muscle function in mice nor is circulating copeptin associated with endothelial function in males or non‐pregnant females. This suggests that adverse vascular effects associated with chronically elevated copeptin concentrations in preeclampsia are more likely a result of the pathophysiological consequences of high AVP rather than copeptin.Support or Funding InformationAPS STRIDE Undergraduate Summer Research Fellowship;AHA 15SFRN23730000;University of Iowa Center for Research by Undergraduates (ICRU); University of Iowa Center for Hypertension Research.