Andrea Kestlerová

Circulating C19MC MicroRNAs in Preeclampsia, Gestational Hypertension, and Fetal Growth Restriction

The objective of the study was to identify the profile of circulating C19MC microRNAs (miR-516-5p, miR-517∗, miR-518b, miR-520a∗, miR-520h, miR-525, and miR-526a) in patients with established preeclampsia (n = 63), fetal growth restriction (n = 27), and gestational hypertension (n = 23). We examined the correlation between plasmatic concentrations and expression levels of microRNAs and the severity of the disease with respect to clinical signs, requirements for the delivery, and Doppler ultrasound parameters. Using absolute and relative quantification approaches, increased extracellular C19MC microRNA levels (miR-516-5p, P = 0.037, P = 0.009; miR-517∗, P = 0.033, P = 0.043; miR-520a∗, P = 0.001, P = 0.009; miR-525, P = 0.026, P = 0.01; miR-526a, P = 0.03, P = 0.035) were detected in patients with preeclampsia. The association analysis pointed to no relationship between C19MC microRNA plasmatic concentrations and expression profile and identified risk factors for a poorer perinatal outcome. However, the dependence between the levels of plasmatic C19MC microRNAs and the pulsatility index in the middle cerebral artery and the values of cerebroplacental ratio was demonstrated. The study brought the interesting finding that the upregulation of miR-516-5p, miR-517∗, miR-520a∗, miR-525, and miR-526a is a characteristic phenomenon of established preeclampsia.

Immunological and biochemical markers in preeclampsia

A basic precondition for the development of preeclampsia is the presence of placental trophoblast cells in the maternal blood circulation. On the other hand, while trophoblast cells are present in the blood of all pregnant women, preeclampsia occurs in only 2-5% of them. Evidently, other factors play a crucial role. The aim of this study was to compare a set of selected immunological factors (anti-cardiolipin autoantibodies, trophoblast-induced cell-mediated immunity, C3 and C4 complement components) and biochemical factors (serum immunoglobulins IgA, IgG, IgM) among three groups of women with uncomplicated pregnancy, gestational hypertension, or preeclampsia. Blood samples were taken 2-12h before delivery. In the preeclampsia group, there was a significantly higher number of women positive for anti-cardiolipin autoantibodies, trophoblast-induced cell-mediated immunity was elevated, serum IgG was elevated and C4 complement component was reduced. We conclude that both elevated autoimmune reactivity and the higher immune reactivity to trophoblast may contribute to the onset of preeclampsia.

Circulating heat shock protein mRNA profile in gestational hypertension, pre-eclampsia & foetal growth restriction

Background & objectives: Heat shock proteins (Hsp) are ubiquitously distributed phylogenetically conserved molecules that regulate cellular homeostasis and maintain the integrity and function of cellular proteins. Increased levels of Hsp in maternal circulation have been shown to be associated with increased risk of pregnancy related complications. The objective of this study was to explore extracellular Hsp mRNA levels in maternal circulation and quantified Hsp27, Hsp60, Hsp70, Hsp90 and Hsp70 binding protein 1 (HspBP1) mRNAs in maternal plasma samples using real-time reverse-transcriptase polymerase chain reaction. Methods: Pregnancies with gestational hypertension (GH) (n = 33), pre-eclampsia (PE) with or without foetal growth restriction (FGR) (n = 78) and FGR (n = 25) were involved in the study. Hsp gene expression was analysed in relation to the severity of the disease with respect to the degree of clinical signs, requirements for the delivery and Doppler ultrasound parameters. Results: Upregulation of Hsp70 was observed in patients with mild and severe PE (P = 0.004 and P = 0.005, respectively) and in pregnancies complicated with PE delivering before and after 34 wk of gestation regardless of the degree of clinical signs (P = 0.015 and P = 0.009, respectively). No difference in the expression of other Hsp genes among the studied groups was observed. No association between Hsp gene expression and Doppler ultrasonography parameters was found. Interpretation & conclusions: These data support that maternal circulation can reflect both maternal and foetal pathologic conditions. Hsp70 represents the sole plasmatic marker, and increased Hsp70 mRNA levels reflect maternal and placental stress response to pregnancy-related complications such as GH and PE, irrespective of the severity of the disease.