FVIIa-antithrombin levels in early and late preeclampsia

Background Preeclampsia (PE) is associated with a hypercoagulability state. According to the gestational age (GA) at the onset of the disease, PE has been classified as early (GA < 34 weeks) and late (GA ≥ 34 weeks). It has been admitted that early PE is associated with ischemic placental lesions, while in late PE an adequate or slightly impaired placentation occurs, which suggests that the two clinical forms have distinct etiology. Tissue factor (TF) binds and activates plasma factor VII triggering the coagulation. The inhibitor antithrombin (AT), along with tissue factor pathway inhibitor, acts as an inhibitor of the FVIIa-TF pathway. Once the TF-FVIIa complex is formed, the binding and transfer of FVIIa to AT is facilitated and FVIIa activity is inhibited. Objective: We evaluated the FVIIa-AT complex levels in pregnant women with early and late severe PE (sPE), in order to verify if this biomarker can be useful for discriminating the two forms of the disease. Methods We evaluated 26 pregnant with severe early PE and 19 pregnant with severe late PE. FVIIa-AT levels were measured by STACLOT® (Diagnostica Stago). Statistical analysis was done by Mann-Whitney test. Results: Increased FVIIa-AT levels were found in early sPE [148.4 pM (137.1)] compared to late sPE [95.9 pM (66.5)] (P = 0.046), which suggests a higher pro-coagulant state when PE onset occurs before 34 weeks of gestation. Conclusion: These pioneer data allow inferring the relevance of FVIIa-AT as a device for early sPE diagnosis. However, the clinical relevance of FVIIa-AT complex surely needs to be fully clarified

Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia.

BACKGROUND: Despite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-β1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE. METHODS: Plasma levels of sEng, TGF-β1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [early (n = 19) and late (n = 24)]. RESULTS: Pregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-β1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-β1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-β1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity. CONCLUSIONS: These results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation

Significant correlations among sEng, TGF-β1, sTNF-R1 and sTNF-R2 levels and laboratorial parameters in preeclamptic women.

<p>The lines represent linear regression and the closed circles represent preeclamptic (PE) women. Maternal plasma sEng concentrations (nanograms/milliliter) are correlated positively with creatinine (mg/dL) (A) and aspartate aminotransferase (U/L) (B) levels in PE women. There is a positive correlation between sTNF-R1 (picograms/milliliter) and lactate dehydrogenase (U/L) levels in PE women (C).</p

Plasma levels of sEng, TGF-β1, sTNF-R1 and sTNF-R2 according to the onset-time and severity of preeclampsia.

<p>Horizontal bars represent median values for sEng and sTNF-R1 and mean values for TGF-β1 and sTNF-R2. **<i>p</i><0.01. Women with late preeclampsia (PE) had higher levels of sTNF-R1 (picograms/milliliter) (C) and sTNF-R2 (picograms/milliliter) (D) than women with early PE. No significant differences were found in sEng (nanograms/milliliter) (A) and TGF-β1 (picograms/milliliter) (B) comparing early and late PE. sEng levels were higher in severe PE than in mild PE (E) and no difference was found for TGF-β1 (F), sTNF-R1 (G) and sTNF-R2 levels (H).</p

Demographic and clinical characteristics of the three studied groups.

<p>Abbreviations: BMI (body mass index: before pregnancy for normotensive pregnant women and preeclamptic women), GWG (gestational weight gain), GA (gestational age), SBP (systolic blood pressure), DPB (diastolic blood pressure), NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women), N/A (not applicable). Note: n =  total subjects.</p>a<p>Data are presented as median (25^th–75^th percentiles); ^bData are presented as mean ± standard deviation; ^cData are presented as number (percentage). ¹Kruskal-Wallis with <i>Bonferroni</i> correction; ²ANOVA with <i>post-hoc</i> LSD;³Pearson chi-square (χ²) test. *<i>p</i><0.05, **<i>p</i><0.017.</p

Plasma levels of sEng, TGF-β1, sTNF-R1 and sTNF-R2 in non-pregnant, normotensive pregnant and preeclamptic women.

<p>NP (non-pregnant women), Norm (normotensive pregnant women), PE (preeclamptic women). Horizontal bars represent median values for sEng, TGF-β1, sTNF-R1 and mean value for sTNF-R2. *<i>p</i><0.05, **<i>p</i><0.01 and ***<i>p</i><0.001. Plasma levels of sEng (nanograms/milliliter) (A), sTNF-R1 (picograms/milliliter) (C) and sTNF-R2 (picograms/milliliter) (D) were higher in normotensive pregnant women than in non-pregnant women. When compared with normotensive pregnant women, sEng (A) and sTNF-R1 (C) were elevated in women with PE. TGF-β1 (picograms/milliliter) levels showed no significant differences among the studied groups (B).</p

Annexin A1 Is Increased in the Plasma of Preeclamptic Women

<div><p>Background</p><p>Preeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties that has been much studied in various animal models of inflammation but poorly studied in the context of human inflammatory diseases. The main objective of this study was to measure AnxA1 levels in PE women and to compare those levels in normotensive pregnant and non-pregnant women. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants.</p><p>Methods</p><p>This study included 40 non-pregnant, 38 normotensive pregnant and 51 PE women. PE women were stratified in early (N = 23) and late (N = 28) subgroups, according to gestational age (GA) at onset of clinical symptoms. Protein AnxA1 and us-CRP plasma levels were determined by ELISA and immunoturbidimetric assays, respectively. Transcript levels of AnxA1 in peripheral blood mononuclear cells (PBMC) were measured by real time RT-PCR.</p><p>Results</p><p>Increased levels of AnxA1 coincided with higher us-CRP levels in the plasma of PE women. Pregnant women with early PE had higher levels of AnxA1 and us-CRP than normotensive pregnant women with GA <34 weeks. No significant difference was found for AnxA1 and us-CRP, comparing late PE and normotensive pregnant women with GA ≥34 weeks. AnxA1 mRNA levels in PBMC were similar among the studied groups. AnxA1 was positively correlated with sTNF-R1, but not with us-CRP.</p><p>Conclusions</p><p>Our data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis. However, more studies are needed to clarify the role of AnxA1 and other proresolving molecules in the context of the systemic inflammatory response in this intriguing disease.</p></div