Immunohistochemical expression of von Willebrand factor in the preeclamptic placenta (original) (raw)
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Aetiology and Physiopathology of Preeclampsia and Related Forms
Acta Clinica Belgica, 2010
Preeclampsia, a pregnancy-specifi c syndrome characterized by hypertension, proteinuria and oedema, resolves on placental delivery. Its pathogenesis is thought to be associated to a hypoxic placenta. Placental hypoxia is responsible for the maternal vascular dysfunction via the increased placental release of anti-angiogenic factors such as soluble fl t1 and endoglin. These soluble receptors bind VEGF, PLGF and TGFβ1 and 3 in the maternal circulation, causing endothelial dysfunction in many maternal tissues. Despite these recent and important new molecular fi ndings, it is important to consider that normal pregnancy is also characterized by systemic infl ammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can produce powerful pro-oxidants that covalently modify proteins and alter vascular function in preeclampsia. Finally, the recent demonstration of activating auto-antibodies to the Angiotensin 1 receptor that experimentally play a major pathogenic role in preeclampsia further indicates the pleiotropism of aetiologies of this condition.
The origins and end-organ consequence of pre-eclampsia
Best Practice & Research Clinical Obstetrics & Gynaecology, 2011
Pre-eclampsia is a multisystem disorder with profound implications for both mother and fetus. Its origins lie in the earliest stages of pregnancy. Abnormal interactions between fetal trophoblast and maternal decidua, including the cells of the maternal immune system, lead to inadequate placental invasion and maternal vascular remodelling. However, abnormal placentation is only one step in the cascade of events that ultimately result in maternal organ dysfunction. Pre-existing maternal conditions predisposing to inflammation and vascular pathology, fetal factors, including multiple gestations and macrosomia, and environmental exposures, including infection, may contribute to the release of placental substances, including anti-angiogenic molecules, into the maternal circulation. These may act directly or indirectly upon the endothelia of end organs, including the kidney, liver and brain. The liberation of reactive oxygen species, cytokines, and microthrombi from damaged endothelia contribute further to organ damage. In studying the normal processes that occur during human placentation and early pregnancy, we will develop a greater understanding of what may go awry in pre-eclampsia. Such research will be crucial in discovering novel biomarkers for prediction of the disorder and, eventually, in finding targets for effective interventions.
[Hemostatic system parameters of placental extracts in normal pregnancy and severe preeclampsia]
Investigación clínica, 2006
To better understand the role of the hemostatic mechanism in preeclampsia, placental extracts obtained from 26 normal pregnant women (NP) and 12 patients with severe pre-eclampsia (SPE) were analyzed to determine thrombomodulin (TM), tissue factor (TF), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) 1 and 2, and TF pathway inhibitor (TFPI). The results showed similar concentrations of TF, TM and PAI-2 in both groups, while tPA increased no significantly and TFPI and PAI-1 increased significantly in SPE placentas.
Preeclampsia is a disorder of pregnancy occurring after midgestation with clinical manifestations of hypertension and proteinuria and has been linked with fetal and maternal morbidity and mortality. Maternal inflammatory syndrome has been associated with preeclampsia. The pathogenetic mechanism proposed behind this syndrome is the maternal endothelial dysfunction caused by atleast of subset of various placental derived factors released into maternal circulation. These are syncytiotrophoblastic microparticles (STBM) or syncytial knots, exosomes or the soluble endoglins. The STBM or the syncytial knots are the end products of trophoblastic life cycle which have been proposed to be altered in the disorder of preeclampsia. So, the aim of the present study was to assess and compare the apoptosis of trophoblastic cells and the syncytial knots in the preeclamptic (20 placentas) and normal (20 placentas) by using TUNEL assay and M30 immunostaining. We also aim to compare various obstetric and clinical parameters affected in preeclampsia (blood pressure, urinary protein, gestational age, birth wt of the babies) between the two groups. In our study, TUNEL Assay as well as M30 immunostaining shows higher trophoblastic as well as syncytial knot apoptotic indices in preeclamptic placentas as compared to normal placentas. The results of our study also show that the clinical parameters (blood pressure, urinary protein) were higher whereas obstetric parameters (gestational age, birth wt of the babies) were lower in preeclamptic patients as compared to controls.
Aspects of inflammation, angiogenesis and coagulation in preeclampsia
Preeclampsia is a major challenge to obstetricians, due to its impact on maternal and fetal morbidity and mortality and the lack of preventive and treatment strategies. The overall aim of this thesis is to increase the knowledge of the pathogenesis of preeclampsia including the role of inflammation, angiogenesis and coagulation, both locally at the fetomaternal interface and in the maternal circulation. Uncompensated maternal endothelial inflammatory responses to factors from stressed trophoblasts seem to be a major contributor to the syndrome, together with an imbalance in angiogenesis and an activated coagulation system. An increasing amount of data indicates an involvement of the immune system with defect tolerance to the conceptus as an integral part of the pathogenesis, at least in early-onset preeclampsia (EOP). We showed that a single administration of human preeclampsia serum in pregnant IL-10 −/− mice induced the full spectrum of preeclampsia-like symptoms including hypoxic injury in uteroplacental tissues and endotheliosis in maternal kidneys. Importantly, preeclampsia serum, as early as 12 to 14 weeks of gestation, disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity (Tube formation test). These results indicate that preeclamptic sera can be used to better understand the pathophysiology and to predict the disorder. Preeclampsia has been associated with increased inflammation, aberrant angiogenesis and activated coagulation, but their correlation and relative contribution are unknown. We found that markers for all these mechanisms were independently associated with preeclampsia. Cytokines, chemokines, and complement factors seem all to be part of a Th1-associated inflammatory reaction in preeclampsia, more pronounced in EOP than in late-onset preeclampsia (LOP), in line with a more homogeneous pathogenesis in EOP as based on placental pathology. In women with intrauterine growth restriction (IUGR), with an anticipated pathologic placentation, only differences in levels for sFlt-1 and PlGF were found in comparison with mothers without IUGR. Thus, sFlt-1 and PlGF seem to be indicators of placental pathology, Results and discussion 4.1 Paper I 4.2 Paper II 4.3 Paper III 4.4 Paper IV 5 Summary and conclusions 6 Future perspectives 7 Acknowledgments 8 References 12
Endothelial function in normal and pre-eclamptic pregnancy: a hypothesis
European Journal of Obstetrics & Gynecology and Reproductive Biology, 1992
Pre-eclampsia is the most common medical complication of pregnancy. Immunologic maladaptation has been suggested to play a role in the etiology of pre-eclampsia. The putative misalliance of fetal trophoblast with maternal tissue in the uteroplacental vascular bed may give rise to an increase in oxygen free radicals. Oxygen free radicals and lipid peroxides might form the link between the hypothetical immunologic maladaptation and the endothelial cell damage known to occur in pre-eclampsia. Recent studies have demonstrated the existence of increased oxygen free radical production in pre-eclampsia. Oxygen free radicals and lipid peroxides decrease vascular prostacyclin and EDRF release and increase thromboxane A, and endothelin release.
Increased VWF antigen levels and decreased ADAMTS13 activity in preeclampsia
Hematology, 2013
This study aimed to assess the von Willebrand factor (VWF) antigen levels and its proteolytic enzyme ADAMTS13 activity in preeclampsia. The study includes 10 non-pregnant women, 50 normal pregnancy, and 110 preeclamptic (PE) women at the same period of pregnancy. For all studied groups plasma ADAMTS13 activities were determined with the FRETs-VWF 73 assay, while VWF antigen levels with an immunoturbometric assay. The plasma ADAMTS13 activity was significantly reduced in PE as compared with normal pregnancy and non-pregnant women (P < 0.01 for both). In contrast, plasma VWF antigen and VWF RCO were significantly elevated in PE, as compared with normal pregnancy group as well as non-pregnant women (P < 0.01 for both). In conclusion, reduction of plasma ADAMTS13 and elevation in VWF might have a role in the pathogenesis of PE.
Early biochemical detection of pre-eclampsia: the role of placental proteins
Immuno-analyse & Biologie Spécialisée, 2004
Pre-eclampsia (PE) is a complex, multisystem pregnancy disorder. Though the maternal symptoms do not occur until late in gestation, there is evidence that the pathology originates in early pregnancy and that factors released from the placenta are responsible for the maternal response. In this study we wanted to compare different placental proteins and growth factors regarding their potential to detect subsequently occurring PE in the early second trimester. In our group of 25 women who later developed mild PE and 64 healthy controls, serum concentrations of six placental and three maternal marker proteins, amongst them pregnancy-associated plasma protein A (PAPP-A), inhibin A and activin A were determined by double-antibody microplate enzyme immunometric assay. PAPP-A and other placental proteins were significantly reduced when compared to the controls. The maternal markers, however, were unaffected which confirms the involvement of the placenta and the usefulness of early biochemical pregnancy testing based on placental proteins.