Alternations of Maternal and Cord Plasma Hemostasis in Preeclampsia Before and After Delivery

Objective: The aim of this study was to investigate the role of hemostatic factors in the pathogenesis of preeclampsia. Materials and Methods: Maternal and cord plasma concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), von willebrand factor (vWF), soluble P-selectin (sP-selectin), fibrinopeptide A (FPA), D-dimer, and antithrombin III (AT-III) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 women with preeclampsia and 40 normotensive pregnant women before and after delivery. Results: The maternal plasma concentrations of TF, vWF, and sP‐selectin were higher, but lower concentrations of TFPI, AT-III, and D-dimer were observed in women with preeclampsia compared to normotensive pregnant women before and after delivery. Compared with maternal plasma, fetal plasma concentrations of TF concentrations were increased significantly in both groups, whereas vWF, FPA, TFPI, AT-III, and D-dimer were decreased. Compared with normotensive pregnancy, fetal plasma concentrations of TF were markedly increased in preeclampsia, accompanied with a higher vWF and a lower sP-selectin and D-dimer levels. Furthermore, fetal plasma TF concentrations were more significantly increased in women with high blood pressure and severe proteinuria. Conclusions: Imbalance in the coagulation/fibrinolysis equilibrium, especially alterations in the extrinsic pathway of coagulation and anticoagulation, may play an important role in the pathogenesis of preeclampsia. In addition, fetal alteration of TF may be involved in the pathogenesis of fetal complications of preeclampsia.     

Comparison of Serum Levels and the Placental Expression of Resistin Between Patients with Preeclampsia and Normal Pregnant Women

Objective. The aim of this study was to evaluate serum resistin levels in women with preeclampsia compared to those in normal pregnant women and normal non-pregnant women, and to examine placental resistin expression. Methods. Serum resistin levels were measured by enzyme-linked immunosorbent assay and placental resistin expression was determined by immunohistochemistry. Results. Serum resistin levels were significantly elevated in women with preeclampsia compared to normal pregnant women and non-pregnant women. There was no significant difference in placental resistin expression. Conclusion. The placenta may not be the origin of the resistin that contributes to increased serum levels in women with preeclampsia.     

Combined biomarkers evaluation for diagnosing kidney injury in preeclampsia

Objective: To identify novel potential biomarkers and evaluate combined biomarkers for diagnosing kidney injury with considerable accuracy in preeclampsia. Methods: The level of serum and urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), retinol-binding protein (RBP) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Results: The level of serum cystatin C, urine RBP, urine NGAL and urine KIM-1 in preeclampsia group were higher than that in the normal pregnancy group. When four biomarkers are combined, the sensitivity and specificity are 100%/98.20%. Conclusion: Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. The more biomarkers combined, the more sensitivity and specificity were increased.     

Prevention of cardiovascular risk in women who had hypertension during pregnancy after 36 weeks gestation

Objective. The aim of our study was to investigate a possible correlation between the expression of the placenta-secreted hormones, β-subunit of human chorionic gonadotrophin (βhCG) and pregnancy-associated plasma protein A (PAPP-A), during the first trimester screening and the development of preeclampsia. Methods. A total of 155 patients between 11 + 0 and 13 + 6 weeks of gestation were enrolled in this study. PAPP-A and βhCG levels were measured using the KRYPTOR® system. Results. The serum levels of βhCG were significantly higher in pregnancies which subsequently developed preeclampsia. The PAPP-A concentration did not differ significantly in pregnancies complicated by preeclampsia than in uncomplicated pregnancies. Conclusion. These results might contribute to developing new tests in the prediction of preeclampsia.     

Risk Factors for a Prolonged Length of Stay in Women Hospitalized for Preeclampsia in Texas

Objectives. To identify correlates of a prolonged length of stay (PLOS) in women hospitalized for preeclampsia/eclampsia in Texas, USA. Methods: Statewide hospital data were obtained, and the records of women who were discharged in 2004 and/or 2005 with a principal discharge diagnosis of preeclampsia or eclampsia were extracted using ICD-9-CM codes. PLOS was defined as a stay greater than 5 days. Odds ratios (OR) for PLOS were calculated. Generalized estimating equations were used to account for a small group of women who were hospitalized multiple times during the study period for preeclampsia. A total of 21,203 records were analyzed. Results: The crude incidence of PLOS was 17.5%. Advancing maternal age was positively associated with PLOS: for every 10-year increase, there was a 20% increase in the odds of PLOS (adjusted OR = 1.20,95% confidence interval (CI): 1.13, 1.28). The strongest risk factor for PLOS was the presence of renal disease: adjusted OR 5.81 (95% CI: 3.97, 8.50). Protective factors included Medicaid beneficiary status, and being admitted from the emergency department. Conclusions: The strongest correlate of PLOS in a large cohort of women hospitalized for preeclampsia was the presence of renal disease.     

Phosphodiesterase Inhibitor Effect on Small Artery Function in Preeclampsia

Objective.?To determine if the phosphodiesterase type 5 inhibitor, sildenafil citrate improves endothelial-dependent relaxation of small arteries from women with preeclampsia.?Methods.?Myometrial and omental biopsies were taken from women participating in a randomized placebo-controlled trial using sildenafil citrate in women with preeclampsia. Vasoconstriction and endothelial-dependent relaxation of small arteries was measured utilizing wire myography.?Results.?Vasoconstriction and endothelial-dependent relaxation of myometrial and omental arteries were not altered in women taking sildenafil.?Conclusion.?Acute effects may have been lost as sildenafil administration occurred many hours prior to myography. Plasma sildenafil levels may have been lower than required for vascular response.     

Dynamic regulation of HIF1Α stability by SUMO2/3 and SENP3 in the human placenta

IntroductionHypoxia-inducible factor 1A (HIF1A) stability is tightly regulated by hydroxylation and ubiquitination. Emerging evidence indicates that HIF1A is also controlled by the interplay between SUMO-specific ligases, which execute protein SUMOylation, and Sentrin/SUMO-specific proteases that de-SUMOylate target proteins. Given the significance of HIF1A in the human placenta, we investigated whether placental HIF1A is subject to SUMOylation in physiological and pathological conditions.MethodsPlacentae were obtained from normal and pregnancies complicated by preeclampsia. Human choriocarcinoma JEG3 cells were maintained at either 21% or 3% oxygen or exposed to sodium nitroprusside (SNP). Cells were transfected with SUMO2/3 constructs with and without Mg132, a proteasome inhibitor. Expression, distribution and associations of SUMO/SENPs and HIF1A were evaluated by Western blotting, immunohistochemistry and co-immunoprecipitation.ResultsHIF1A-SUMO2/3 associations peaked at 9–10 weeks, while its deSUMOylation by SENP3 was greatest at 10–12 weeks. In E-PE, HIF1A deSUMOylation by SENP3 was significantly elevated, while HIF1A-SUMO2/3 associations remained constant. In vitro, overexpression of SUMO2/3 de-stabilized HIF1A in hypoxia, and abrogated HIF1A expression following Mg132 treatment in normoxia. Hypoxia and SNP treatments promoted SENP3 nuclear redistribution from nucleoli to the nucleoplasm where it associates with HIF1A.ConclusionDuring early placental development, SUMOylation events control HIF1A stability in an oxygen-dependent manner. In E-PE, enhanced deSUMOylation of HIF1A by SENP3 may in part contribute to increased HIF1A activity and stability found in this pathology.     

Role of microparticles in recurrent miscarriages and other adverse pregnancies: a review

The multiple functions attributed to microparticles (MPs) include blood coagulation, inflammation, tumorigenesis, angiogenesis, immunomodulatory functions and intercellular cross talk. These have drawn considerable interest during the last few years. The prothrombotic nature of MPs has linked them with almost all groups of thrombotic disorders including recurrent miscarriage (RM) and other abnormal pregnancy outcomes. Two authors (SS and RP) conducted a search independently on the computerized databases MEDLINE and EMBASE using relevant key words. Contradictory reports were observed on the association of MPs with RM. While most of the reports showed increased prevalence of MPs, both platelet and endothelial cell derived, in RM, some did not show any association. Almost all the reports showed a strong association of MPs with preeclampsia (PE), while the association with other adverse pregnancy conditions was not very conclusive. It may be concluded that MPs by themselves may result in adverse conditions or that they may be additive factors to an already existing prothrombotic state due to acquired or genetic thrombophilia or some unknown thrombophilic condition, besides the pre-existing hypercoagulable status of pregnancy.     

The Effects of Preeclampsia and Oxygen Environment on Endothelial Release of Matrix Metalloproteinase‐2

Background: There is evidence of altered vascular endothelial function in women with preeclampsia as well as in the endothelial cells from umbilical vessels of preeclamptic pregnancies. Matrix metalloproteinase (MMP)‐2 is elevated in the plasma of preeclamptic women and is a mediator of vascular reactivity; however, whether MMP‐2 release is altered in preeclamptic endothelial cells is unknown. We hypothesize that MMP‐2 release is enhanced in endothelial cells from preeclamptic compared with uncomplicated pregnancies and that this phenomenon may be mediated by an oxygen‐dependent mechanism. Our specific hypothesis is that cells from normal pregnancies will demonstrate enhanced MMP‐2 release at low oxygen (< 0.5%, 2%) compared to high oxygen (20%), thus mimicking the behavior of preeclamptic cells. Methods: Human umbilical vein endothelial cells (HUVECs) from preeclamptic pregnancies (n = 4) and normal pregnancies (n = 4) were incubated for 12 hr in standard culture conditions (20% oxygen). In a separate series of experiments, HUVECs from normal pregnancies (n = 6) were incubated for 12 hr at < 0.5%, 2%, and 20% oxygen. Supernatants were analyzed for MMP‐2 and tissue inhibitors of metalloproteinases (TIMP)‐1 and ‐2. Results: The HUVECs from women with preeclampsia demonstrated significantly enhanced release of MMP‐2 (p < 0.05), TIMP‐1 (p < 0.001), and TIMP‐2 (p = 0.01) compared to normal cells. MMP‐2 release from HUVECs from uncomplicated pregnancies was significantly elevated at 2% oxygen compared to < 0.5% and 20% oxygen (p < 0.05). TIMP‐1 and ‐2 secretion was not altered with varying oxygen. Conclusions: Preeclamptic endothelial cells demonstrate significantly enhanced MMP‐2, TIMP‐1 and TIMP‐2 release compared to normal cells. Our data show that there are significant effects of oxygen tension on MMP‐2 release from normal cells; however, the magnitude of the enhanced release is small when compared to the differences in MMP‐2 release in cells from preeclamptic and normal pregnancies. Furthermore, TIMP‐1 and ‐2 release is not affected by changes in oxygen. It is unlikely that oxygen is a key mediator of the enhanced MMP‐2, TIMP‐1 and TIMP‐2 release observed in preeclamptic cells.     

Late Onset Preeclampsia is not an Innocuous Condition

Objective: To describe the profile and outcome of late-onset preeclampsia (LOPE). Methods. Retrospective study of 264 singleton pregnancies presenting before delivery at two referral centres in South Africa. Results: Primigravid patients constituted 56.8% of the group, while 57.6% were graded as severe. Median gestational age at diagnosis was 37 (34–43) weeks. 30.7% of patients experienced ≥1 major maternal complication including 34 (12.9%) cases of eclampsia. There were no maternal or early neonatal deaths. Five intrauterine deaths occurred, all due to placental abruption. The perinatal mortality rate was 18.9 per thousand births. Conclusions: Late-onset preeclampsia often presents as severe disease.