Az ösztrogén receptor gén polimorfizmus és a lipoproteinek, valamint egyes alvadási tényezők kapcsolata. Az ösztrogén receptor gén polimorfizmus szerepe a cardiovascularis betegségek rizikójában = Association of estrogen receptor gene polymorphisms with serum lipoprotein levels and hemostatic factors. The role of estrogen receptor gene polymorphisms in the risk of cardiovascular diseases

Az ösztrogének az ösztrogén receptor ?-n keresztül számos (részben lokális, részben szisztémás) hatást gyakorolnak a cardiovascularis rendszerre. Kutatási projektünk keretében azt vizsgáltuk, hogy az ösztrogén receptor ? gén PvuII (ESR1c.454-397T>C) és XbaI (ESR1c.454-351A>G) polimorfizmusa mutat-e összefüggést az ischaemiás stroke, a koszorúér betegség és a praeeclampsia kockázatával, illetve, hogy befolyásol-e ösztrogén-függő lipid, alvadási és gyulladásos tényezőket reproduktív korú, egészséges egyénekben. Tanulmányunkban az ösztrogén receptor ? PvuII és XbaI polimorfizmusa és az ischaemiás stroke, illetve koszorúér betegség között nem találtunk asszociációt. Az XbaI polimorfizmus azonban összefüggést mutatott a szérum lipoprotein(a) szintekkel reproduktív korú egészséges egyénekben. Reproduktív korú egészséges nőkben a PvuII polimorfizmus a szérum összkoleszterin, míg az XbaI polimorfizmus a szérum összkoleszterin és LDL-koleszterin szintekkel mutatott asszociációt. Terhességben a T-A haplotípus homozigóta hordozóinak rizikója szignifikánsan nagyobb volt praeeclampsiára a más genotípus-kombinációt hordozókkal összehasonlítva. Praeeclampsiás terhesekben az ESR1 XbaI polimorfizmus az intrauterin növekedési retardatióval mutatott összefüggést. A két polimorfizmus szérum lipid szintekre, valamint a praeeclampsia és a magzati sorvadás kockázatára gyakorolt hatásának pontos molekuláris mechanizmusa azonban még nem ismert. | Estrogen has several ESR1-mediated effects - including both direct effects and systemic effects - on the cardiovascular system. The aim of our research project was to determine whether two polymorphisms of the ESR1 gene (ESR1 c.454-397T>C: PvuII restriction site and c.454-351A>G: XbaI restriction site) are associated with ischemic stroke, coronary artery disease or preeclampsia. We also investigated whether these polymorphisms can influence estrogen-dependent lipid, haemostatic and inflammatory variables in healthy Caucasian women and men of reproductive age. According to our results, the ESR1 PvuII and XbaI polymorphisms were not associated with ischemic stroke or coronary artery disease. In healthy subjects of reproductive age, the ESR1 XbaI polymorphism affected serum lipoprotein(a) concentrations. In healthy women of reproductive age, the PvuII polymorphism was associated with serum total cholesterol levels, whereas the XbaI polymorphism affected serum total cholesterol and LDL cholesterol concentrations. In pregnancy, the homozygous T-A haplotype carriers of ESR1 PvuII and XbaI polymorphisms showed an increased risk of preeclampsia. In addition, the ESR1 XbaI polymorphism was associated with fetal growth restriction in preeclamptic patients. However, the molecular mechanisms by which the two polymorphisms affect serum lipid levels and the risk of preeclampsia and fetal growth restriction are still unclear

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. Orv. Hetil., 2014, 155(47), 1860-1866

Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array

<p>Abstract</p> <p>Background</p> <p>Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Cytokines, chemokines and adhesion molecules are central to innate and adaptive immune processes. The purpose of this study was to determine circulating levels of cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia in a comprehensive manner, and to investigate their relationship to the clinical features and laboratory parameters of the study participants, including markers of overall inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) and endothelial injury (fibronectin), oxidative stress (malondialdehyde) and trophoblast debris (cell-free fetal DNA).</p> <p>Results</p> <p>Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were measured in 60 preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by multiplex suspension array and ELISA. In normal pregnancy, the relative abundance of circulating IL-18 over IL-12p70 and the relative deficiency of the bioactive IL-12p70 in relation to IL-12p40 might favour Th2-type immunity. Although decreased IL-1ra, TNF-alpha and MCP-1 concentrations of healthy pregnant relative to non-pregnant women reflect anti-inflammatory changes in circulating cytokine profile, their decreased serum IL-10 and increased IP-10 levels might drive pro-inflammatory responses. In addition to a shift towards Th1-type immunity (expressed by the increased IL-2/IL-4 and IFN-gamma/IL-4 ratios), circulating levels of the pro-inflammatory cytokines IL-6 and TNF-alpha, the chemokines IL-8, IP-10 and MCP-1, as well as the adhesion molecules ICAM-1 and VCAM-1, were raised in preeclampsia compared with healthy pregnancy, resulting in an overall pro-inflammatory systemic environment. Increased IP-10, MCP-1, ICAM-1 and VCAM-1 concentrations of preeclamptic patients showed significant correlations with blood pressure values, renal and liver function parameters, as well as with CRP, malondialdehyde, von Willebrand factor antigen and fibronectin levels.</p> <p>Conclusions</p> <p>According to our findings, preeclampsia was associated with an overall pro-inflammatory systemic environment. Elevated amounts of pro-inflammatory cytokines, chemokines and adhesion molecules in the maternal circulation might play a central role in the excessive systemic inflammatory response, as well as in the generalized endothelial dysfunction characteristics of the maternal syndrome of preeclampsia.</p

Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia.

The activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease is low in several conditions, including HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome. As HELLP syndrome develops in most cases on the basis of preeclampsia, our aim was to determine whether plasma ADAMTS13 activity is decreased in preeclampsia. Sixty-seven preeclamptic patients, 70 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Plasma ADAMTS13 activity was determined with the FRETS-VWF73 assay, while VWF antigen (VWF:Ag) levels with an enzyme-linked immunosorbent assay. The multimeric pattern of VWF was analyzed by SDS-agarose gel electrophoresis. There was no significant difference in plasma ADAMTS13 activity between the preeclamptic and the healthy pregnant and non-pregnant groups (median [25-75 percentile]: 98.8 [76.5-112.8] %, 96.3 [85.6-116.2] % and 91.6 [78.5-104.4] %, respectively; p > 0.05). However, plasma VWF:Ag levels were significantly higher in preeclamptic patients than in healthy pregnant and non-pregnant women (187.1 [145.6-243.1] % versus 129.3 [105.1-182.8] % and 70.0 [60.2-87.3] %, respectively; p < 0.001). The multimeric pattern of VWF was normal in each group. Primiparas had lower plasma ADAMTS13 activity than multi-paras (92.6 [75.8-110.6] % versus 104.2 [92.1-120.8] %; p = 0.011). No other relationship was found between clinical characteristics, laboratory parameters and plasma ADAMTS13 activity in either study group. In conclusion, plasma ADAMTS13 activity is normal in preeclampsia despite the increased VWF:Ag levels. However, further studies are needed to determine whether a decrease in plasma ADAMTS13 activity could predispose preeclamptic patients to develop HELLP syndrome

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

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Increased circulating interleukin-17 levels in preeclampsia

Increasing evidence suggests that an exaggerated maternal systemic inflammatory response, as well as an angiogenic imbalance plays a central role in the pathogenesis of preeclampsia. In this study, we determined circulating levels of interleukin-17 (IL-17) along with those of angiogenic factors in healthy non-pregnant and pregnant women and preeclamptic patients, and examined whether serum IL-17 levels of preeclamptic patients were related to their clinical features and angiogenic factor concentrations. Fifty-nine preeclamptic patients, 60 healthy pregnant women and 56 healthy non-pregnant women were involved in this case-control study. Serum levels of IL-17A were measured by high sensitivity ELISA. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Serum IL-17 levels were significantly higher in preeclamptic patients than in healthy non-pregnant and pregnant women. We did not find any relationship between serum IL-17 concentrations of preeclamptic patients and their clinical features and serum sFlt-1 and PlGF levels or sFlt-1/PlGF ratios. However, elevated serum IL-17 level and sFlt-1/PlGF ratio was found to be additive for the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone. In conclusion, serum IL-17 levels are increased in preeclampsia, which might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease. In addition, elevated serum IL-17 level and sFlt-1/PlGF ratio had an additive (joint) effect in the risk of preeclampsia

A vérplazma összes szabad DNS, valamint szabad magzati DNS mennyisége praeeclampsiával szövődött és szövődménymentes terhességek esetében = Quantity of total cell free and cell free fetal DNA in pregnancies with no complications and with preeclampsia

A plazmában keringő szabad DNS minőségi és mennyiségi vizsgálata mint a praenatalis diagnosztika lehetséges eszköze egy évtizedes múltra tekint vissza. Az általunk végzett vizsgálat célja az összes szabad DNS, valamint szabad magzati DNS mennyiségének vizsgálata volt szövődménymentes, illetve praeeclampsiával szövődött terhességek esetén. Módszerek: A vizsgálatot retrospektív módon végeztük. Klinikánkon megjelent és kezelés alatt álló 67 praeeclampsiával szövődött, illetve 70 szövődménymentes terhességet viselő várandós nőtől gyűjtöttünk vérplazmát. A keringő összes szabad DNS és szabad magzati DNS meghatározását valós idejű polimeráz láncreakcióval (real-time PCR) végeztük. Eredmények: A plazma szabad DNS, valamint a szabad magzati DNS mennyisége egyaránt szignifikánsan magasabb volt praeeclampsiás terhesek esetében (medián: 0,0114 vs. 0,0325 és 0,001 E-3 vs. 0,086 E-3 ng/μl; P < 0,001). Az összes szabad DNS, valamint a szabad magzati DNS mennyisége között, illetve a testtömegindex között nem találtunk szignifikáns összefüggést. Következtetés: A praeeclampsia hátterében feltételezett kórfolyamatok, a placentáció zavara, endothel- és hepatocellularis károsodás nagy valószínűséggel egyaránt befolyásolja az összes szabad DNS mennyiségének emelkedését. A szabad magzati DNS mennyiségének emelkedése a trophoblastinvázió zavarának mutatójaként lehetséges markerként jön szóba a praeeclampsia korai diagnosztizálásában. | Several researches focused on the factors which could influence the quantity of cell free DNA in case of normal and pathological pregnancies. The aim of our study was to evaluate the quantity of total cell free and cell free fetal DNA in case of normal pregnancies and preeclampsia. Study design: Plasma samples were obtained from 67 preeclamptic and 70 normotensive pregnant women. The quantity of total cell free DNA and cell free fetal DNA was measured using real-time polymerase chain reaction. Results: We confirmed that circulating total free and fetal DNA levels are significantly elevated in pregnancies complicated by preeclampsia (median: 0.0114 vs. 0.0325 and 0.001E-3 vs. 0.086E-3 ng/μl; P < 0.001). The quantity of total plasma-free DNA did not correlate with the body mass index. Conclusion: The releases of both free fetal and maternal DNA were found to be affected in preeclampsia. Hepatocellular necrosis seems to be responsible - at least partly - for increased circulating total DNA levels in preeclampsia, and the abnormal trophoblast invasion could be responsible for increased trophoblast destruction and elevation of cell free fetal DNA level