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

Abstract

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.

Figure 1. Plasma levels of sEng, TGF-β1, sTNF-R1 and sTNF-R2 in non-pregnant, normotensive pregnant and preeclamptic women.

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. *p<0.05, **p<0.01 and ***p<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).

Figure 2. Plasma levels of sEng, TGF-β1, sTNF-R1 and sTNF-R2 according to the onset-time and severity of preeclampsia.

Horizontal bars represent median values for sEng and sTNF-R1 and mean values for TGF-β1 and sTNF-R2. **p<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).

Figure 3. Significant correlations among sEng, TGF-β1, sTNF-R1 and sTNF-R2 levels and clinical parameters in preeclamptic women.

The lines represent linear regression and the closed circles represent preeclamptic (PE) women. Maternal plasma sEng concentrations (nanograms/milliliter) are correlated negatively with gestational age (A), while a positive correlation was found between sTNF-R1 (picograms/milliliter) (B) and sTNF-R2 (picograms/milliliter) (C) plasma levels and gestational age in PE women. sEng plasma levels are also correlated positively with systolic blood pressure in PE women (D).

Figure 4. Significant correlations among sEng, TGF-β1, sTNF-R1 and sTNF-R2 levels and laboratorial parameters in preeclamptic women.

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).