Bálint Alasztics

[The pathophysiology of preeclampsia in view of the two-stage model].

Preeclampsia is a common and severe disease in pregnancy, a major cause of maternal and fetal morbidity and mortality. The main features of the disease are de novo hypertension after the 20th gestational week and proteinuria, and it is frequently accompanied by edema and other subjective symptoms. The origin of the disease is the placenta, but its sequelae affect multiple organ systems. According to the two-stage model of preeclampsia, the abnormal and hypoperfused placenta (stage 1) releases factors to the bloodstream, which are responsible for the maternal symptoms (stage 2). Oxidative stress, impaired function of nitric-oxide synthase, cellular and humoral immunological factors play an important role in the pathophysiology of the placenta. Endothelial dysfunction is the common denominator of the clinical symptoms. The theory explains the origins of hypertension, proteinuria, edema and other symptoms as well.

Various levels of circulating exosomal total-miRNA and miR-210 hypoxamiR in different forms of pregnancy hypertension

INTRODUCTION Hypertension is a common complication during pregnancy, affecting 10% of pregnant women worldwide. Several microRNA (miRNA) were shown to be involved in hypertensive disorders of pregnancy. In preeclampsia (PE), placental dysfunction causes the enhanced release of extracellular vesicle-derived miRNAs. The hypoxia-sensitive hsa-mir-210 is the most common PE-associated miRNA, but its exosomal profile has not been investigated. OBJECTIVES Our aims were to measure exosomal total-miRNA concentration and to perform expression analysis of circulating exosomal hsa-miR-210 in women affected by chronic hypertension (CHT) gestational hypertension (GHT) or PE. MATERIALS AND METHODS We collected plasma samples from women with CHT, GHT, PE (moderate: mPE and severe: sPE) and from normotensive pregnancies. Exosomal miRNAs were extracted and miRNA concentration was measured. RT-PCR was carried out with hsa-miR-210-3p-specific primers and relative expression was calculated using the comparative Ct method. RESULTS The total-miRNA concentration was different in the disease subgroups, and was significantly higher in mPE and sPE compared to the other groups. We found a significant difference in the relative exosomal hsa-miR-210-3p expression between all hypertensive groups compared to the normotensive samples, but significant upregulation was only observed in case of mPE and sPE patients. Both the level of total-miRNA and hsa-miR-210 expression was higher in case of severe PE. CONCLUSIONS The level of circulating exosomal total-miRNA and hsa-miR-210 was elevated in women with PE, and it was higher in the severe form. We showed that hsa-miR-210 is secreted via exosomes, which may have a role in the pathomechanism of the disease.

The role of angiogenic factors in preeclampsia

Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia.A praeeclampsia az egyik leggyakoribb es legsulyosabb terhessegi korkep, kezelese a mai napig a szuleszet nagy kihivasa. A korkep pontos etiologiaja az elmult evtizedek kutatasainak ellenere nem kellően tisztazott. A 2000-es evek elejen a praeeclampsia korelettananak kutatasa az angiogenezist befolyasolo faktorok fele iranyult. A legtobbet vizsgalt molekula a mehlepenyi eredetű novekedesi faktor es a szolubilis fms-like tirozin-kinaz-1, amelyek szerepet a betegseg patomechanizmusaban szamos tanulmany igazolta. Az eddigi vizsgalatok az antiangiogen faktorok szintjenek emelkedeset es a proangiogen faktorok szintjenek csokkeneset mutattak ki mar a praeeclampsia klinikai tuneteinek megjelenese előtt. Jelenlegi ismereteink szerint az antiangiogen feherjek tehetők felelősse a praeeclampsiaban kialakulo endothelkarosodasert. A mehlepenyi eredetű novekedesi faktornak es a szolubilis fms-like tirozin-kinaz-1-nek a betegseg előrejelzeseben es kezeleseben fontos szerepe lehet. A ket feherje szerumszintjenek meghatarozasara gyorstesztek allnak rendelkezesunkre. Az antiangiogen hatasu szolubilis fms-like tirozin-kinaz-1-nek az anyai verkeringesből tortenő kivonasa uj terapias lehetőseget jelenthet a jovőben a praeeclampsias betegek szamara.

Screening of trisomy 21 nowadays. Is maternal age so important

INTRODUCTION Trisomy 21 is the most common chromosomal abnormality, therefore, screening and diagnosis of this disorder is in the centre of attention worldwide. An efficient screening method is the combined test based on maternal age, ultrasound signs, biochemical markers, and a risk ratio can be calculated based on these data. AIM The aim of the authors was to determine the causes of missed prenatal diagnosis of Downs syndrome at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. METHOD A retrospective study was carried out by collecting data from medical records of mothers who had delivered a newborn with Downs syndrome in the Department between 2008 and 2012. Each medical record was analyzed individually. RESULTS In most cases the missed diagnosis of Downs syndrome occurred when the expectant mother failed to attend the first trimester screening or did not take the risk of invasive diagnostic procedures needed for fetal kariotyping. CONCLUSIONS Analysis of fetal DNA circulating in maternal plasma can be a solution for those who refuse invasive fetal diagnostics. This test has high sensitivity and very low false positive rate. It has become available since the end of 2011 in the United States and, since the autumn of 2012, in Hungary, too. The test, however, is not reimbursed by national health insurance.

A 21-es triszómia szűrése napjainkban. Az anyai életkor valóban olyan fontos? [Screening of trisomy 21 nowadays. Is maternal age so important?]

INTRODUCTION Trisomy 21 is the most common chromosomal abnormality, therefore, screening and diagnosis of this disorder is in the centre of attention worldwide. An efficient screening method is the combined test based on maternal age, ultrasound signs, biochemical markers, and a risk ratio can be calculated based on these data. AIM The aim of the authors was to determine the causes of missed prenatal diagnosis of Downs syndrome at the 2nd Department of Obstetrics and Gynecology, Semmelweis University. METHOD A retrospective study was carried out by collecting data from medical records of mothers who had delivered a newborn with Downs syndrome in the Department between 2008 and 2012. Each medical record was analyzed individually. RESULTS In most cases the missed diagnosis of Downs syndrome occurred when the expectant mother failed to attend the first trimester screening or did not take the risk of invasive diagnostic procedures needed for fetal kariotyping. CONCLUSIONS Analysis of fetal DNA circulating in maternal plasma can be a solution for those who refuse invasive fetal diagnostics. This test has high sensitivity and very low false positive rate. It has become available since the end of 2011 in the United States and, since the autumn of 2012, in Hungary, too. The test, however, is not reimbursed by national health insurance.

The impact of circulating preeclampsia-associated extracellular vesicles on the migratory activity and phenotype of THP-1 monocytic cells

Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. We hypothesized that preeclampsia-associated EVs (PE-EVs) induced functional and phenotypic alterations of monocytes. First, we proved EV binding and uptake by THP-1 cells. Cellular origin and protein cargo of circulating PE-EVs were characterized by flow cytometry and mass spectrometry. An altered phagocytosis-associated molecular pattern was found on 12.5 K fraction of PE-EVs: an elevated CD47 “don’t eat me” signal (p < 0.01) and decreased exofacial phosphatidylserine “eat-me” signal (p < 0.001) were found along with decreased uptake of these PE-EVs (p < 0.05). The 12.5 K fraction of PE-EVs induced significantly lower chemotaxis (p < 0.01) and cell motility but accelerated cell adhesion of THP-1 cells (p < 0.05). The 12.5 K fraction of PE-EVs induced altered monocyte functions suggest that circulating EVs may have a role in the pathogenesis of preeclampsia.

Author Correction: The impact of circulating preeclampsia-associated extracellular vesicles on the migratory activity and phenotype of THP-1 monocytic cells

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Az angiogén faktorok szerepe praeeclampsiában

Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia.A praeeclampsia az egyik leggyakoribb es legsulyosabb terhessegi korkep, kezelese a mai napig a szuleszet nagy kihivasa. A korkep pontos etiologiaja az elmult evtizedek kutatasainak ellenere nem kellően tisztazott. A 2000-es evek elejen a praeeclampsia korelettananak kutatasa az angiogenezist befolyasolo faktorok fele iranyult. A legtobbet vizsgalt molekula a mehlepenyi eredetű novekedesi faktor es a szolubilis fms-like tirozin-kinaz-1, amelyek szerepet a betegseg patomechanizmusaban szamos tanulmany igazolta. Az eddigi vizsgalatok az antiangiogen faktorok szintjenek emelkedeset es a proangiogen faktorok szintjenek csokkeneset mutattak ki mar a praeeclampsia klinikai tuneteinek megjelenese előtt. Jelenlegi ismereteink szerint az antiangiogen feherjek tehetők felelősse a praeeclampsiaban kialakulo endothelkarosodasert. A mehlepenyi eredetű novekedesi faktornak es a szolubilis fms-like tirozin-kinaz-1-nek a betegseg előrejelzeseben es kezeleseben fontos szerepe lehet. A ket feherje szerumszintjenek meghatarozasara gyorstesztek allnak rendelkezesunkre. Az antiangiogen hatasu szolubilis fms-like tirozin-kinaz-1-nek az anyai verkeringesből tortenő kivonasa uj terapias lehetőseget jelenthet a jovőben a praeeclampsias betegek szamara.

Az angiogén faktorok szerepe praeeclampsiában | The role of angiogenic factors in preeclampsia

Preeclampsia is one of the most common and most serious complications of pregnancy and the management of this condition still challenges obstetricians. Despite intensive research the etiology of preeclampsia still remains unclear. At the beginning of the 2000s preeclampsia-related research was directed towards factors that influence angiogenesis. Most studies have been carried out on the placental growth factor and soluble fms-like tyrosine kinase-1. Most publications confirm the increased concentrations of antiangiogenic factors and decreased concentrations of proangiogenic factors in maternal blood samples in preeclampsia even before the onset of clinical symptoms. According to our current knowledge antiangiogenic proteins are responsible for the endothelial dysfunction in the symptomatic stage of the disease. Placental growth factor and soluble fms-like tyrosine kinase-1 may have important roles in the prediction and treatment of the disease. The point of care detection of placental growth factor and soluble fms-like tyrosine kinase-1 may be used to predict preeclampsia. Rapid tests are available to determine the serum levels of the two proteins. Removal of soluble fms-like tyrosine kinase-1 from maternal circulation is a potential treatment option for early onset preeclampsia.A praeeclampsia az egyik leggyakoribb es legsulyosabb terhessegi korkep, kezelese a mai napig a szuleszet nagy kihivasa. A korkep pontos etiologiaja az elmult evtizedek kutatasainak ellenere nem kellően tisztazott. A 2000-es evek elejen a praeeclampsia korelettananak kutatasa az angiogenezist befolyasolo faktorok fele iranyult. A legtobbet vizsgalt molekula a mehlepenyi eredetű novekedesi faktor es a szolubilis fms-like tirozin-kinaz-1, amelyek szerepet a betegseg patomechanizmusaban szamos tanulmany igazolta. Az eddigi vizsgalatok az antiangiogen faktorok szintjenek emelkedeset es a proangiogen faktorok szintjenek csokkeneset mutattak ki mar a praeeclampsia klinikai tuneteinek megjelenese előtt. Jelenlegi ismereteink szerint az antiangiogen feherjek tehetők felelősse a praeeclampsiaban kialakulo endothelkarosodasert. A mehlepenyi eredetű novekedesi faktornak es a szolubilis fms-like tirozin-kinaz-1-nek a betegseg előrejelzeseben es kezeleseben fontos szerepe lehet. A ket feherje szerumszintjenek meghatarozasara gyorstesztek allnak rendelkezesunkre. Az antiangiogen hatasu szolubilis fms-like tirozin-kinaz-1-nek az anyai verkeringesből tortenő kivonasa uj terapias lehetőseget jelenthet a jovőben a praeeclampsias betegek szamara.