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Abstract Preeclampsia (PE) is a serious gestational complication affecting the life of a mother and child. The immunophenotype and gene expression profile of isolated blood monocyte subpopulations of pregnant women with PE have not been studied before. In this work, we assessed changes in CD14++ and CD16++ monocyte subpopulations in PE and physiological pregnancy (n = 33). Immunophenotyping, immunomagnetic sorting of monocytes and analysis of the transcriptional profile of their genes were carried out. The percentage of classical monocytes was significantly lower, while the intermediate fraction of monocytes was significantly higher in late-onset PE compared to control. Transcriptome analysis of late-onset PE classical CD14++ monocytes revealed significant activation of inflammation mediated by chemokine and cytokine signalling pathways; apoptosis; regulation of transcription from RNA polymerase II promoter in response to stress and others. The most suppressed signalling pathways were associated with T cell activation and selection. In CD16++ monocytes of late-onset PE cases, positive regulation of cell–cell adhesion, integrin signalling pathway, blood coagulation cascade were the most activated ones. The inflammation mediated by chemokine and cytokine signalling pathway and p53 pathway were the most down-regulated in CD16++ monocytes. The obtained results indicate profound changes occurring to two most polar monocyte subpopulations in PE and their different roles in the pathogenesis of this disease.

Antihypertensive therapy is an essential part of management of patients with preeclampsia (PE). Methyldopa (Dopegyt®) and nifedipine (Cordaflex®) are basic medications of therapy since they stabilize blood pressure without affecting the fetus. Their effect on the endothelium of placental vessels has not yet been studied. In this study, we analyzed the effect of antihypertensive therapy on the expression of fucosylated glycans in fetal capillaries of placental terminal villi in patients with early-onset PE (EOPE) and late-onset PE (LOPE), and determined correlation between their expression and mother's hemodynamic parameters, fetoplacental system, factors reflecting inflammatory response, and destructive processes in the endothelial glycocalyx (eGC). A total of 76 women were enrolled in the study: the comparison group consisted of 15 women with healthy pregnancy, and the main group comprised 61 women with early-onset and late-onset PE, who received one-component or two-component antihypertensive therapy. Hemodynamic status was assessed by daily blood pressure monitoring, dopplerometry of maternal placental and fetoplacental blood flows, and the levels of IL-18, IL-6, TNFα, galectin-3, endocan-1, syndecan-1, and hyaluronan in the blood of the mother. Expression of fucosylated glycans was assessed by staining placental sections with AAL, UEA-I, LTL lectins, and anti-LeY MAbs. It was found that (i) expression patterns of fucosylated glycans in eGC capillaries of placental terminal villi in EOPE and LOPE are characterized by predominant expression of structures with a type 2 core and have a similar pattern of quantitative changes, which seems to be due to the impact of one-component and two-component antihypertensive therapy on their expression; (ii) correlation patterns indicate interrelated changes in the molecular composition of eGC fucoglycans and indicators reflecting changes in maternal hemodynamics, fetoplacental hemodynamics, and humoral factors associated with eGC damage. The presented study is the first to demonstrate the features of placental eGC in women with PE treated with antihypertensive therapy. This study also considers placental fucoglycans as a functional part of the eGC, which affects hemodynamics in the mother–placenta–fetus system. [ABSTRACT FROM AUTHOR]

Fetal arrhythmia develops in 0.1–5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed. [ABSTRACT FROM AUTHOR]

This paper provides an assessment of molecular and functional changes in blood vessels, and a description of vascular patterns during preeclampsia (PE). Patients with normal pregnancy, and pregnancy complicated by PE at earlier (20–34 weeks) and later terms (≥34 weeks) underwent a 24 h monitoring of blood pressure, central hemodynamics, arterial stiffness, and myocardial function. The blood levels of the structural components of endothelial glycocalyx (eGC): syndecan-1 (SDC 1), heparan sulfate proteoglycan 2 (HSPG2), and hyaluronic acid (HA) were determined. In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes, probably leading to more severe course of PE and the formation of morphological grounds for cardiovascular disorders. The vascular pattern in late-onset PE, including changes in HA levels, central hemodynamics, and myocardial function, may be a signal of potential cardiovascular disorder. PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium, with its subsequent hypertrophy and decompensation, leading to a delayed development of cardiovascular disorders after PE. Further clinical studies of these indicators will possibly identify predictors of PE and long-term consequences of the disease. [ABSTRACT FROM AUTHOR]

Background: PE is present in ∼2-8% of all pregnant women worldwide. Placental bed disorders at early and late PE have been not carried out yet. However, these studies help to explore details of the pathogenesis of PE, and to optimize the prognosis and obstetric management.Objective: To identify clinical and morphological differences between early- and late-onset PE based on a comprehensive observation of pregnant women with regard to morphological and immunohistochemical characteristics of the placental bed.Materials and Methods: One hundred fifty patients aged 18-43 years old delivered by cesarean section due to severe PE. The samples of placental bed tissue were studied by morphological and immunohistochemical methods.Results: The violation of invasion trophoblast, remodeling of spiral arteries were expressed in early onset PE; the degree of compensation of chronic hypoxia tissue in the area of the placental site was typical for late PE and was absent of an early onset PE.Conclusion: Our studies confirm the need for separation of early- and late-onset PE, being justified in terms of different pathogenetic mechanisms of formation, and therefore the possibility of therapeutic effects, duration of pregnancy prolongation, forecasting, search early diagnostic markers of the disease, and personalized approaches. [ABSTRACT FROM AUTHOR]

Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]