Soluble Endoglin, Transforming Growth Factor-Beta 1 and Soluble Tumor Necrosis Factor Alpha Receptors in Different Clinical Manifestations of Preeclampsia

Abstract

BackgroundDespite 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.MethodsPlasma 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)].ResultsPregnancy 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.ConclusionsThese 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.

Pre‐eclampsia is associated with reduced resolvin D1 and maresin 1 to leukotriene B4 ratios in the plasma

“…lated, while anti-inflammatory cytokine IL-10 was downregulated in PE 22,27,28. The pro-inflammatory lipid mediator LTB4 was increased in the plasma of PE women compared with normotensive pregnant women in the current study.…”

“…17,18 In this sense, it is widely accepted that normotensive pregnancy is physiologically associated with a higher pro-inflammatory status when compared to the non-pregnant state. 21,22 LTB4 is a lipid mediator endowed with pro-inflammatory activities. 21,22 LTB4 is a lipid mediator endowed with pro-inflammatory activities.…”

IL-10 supplementation increases Tregs and decreases hypertension in the RUPP rat model of preeclampsia

“…While the data regarding levels of circulating TGF-β during PE is not consistent, some studies have shown the cytokine to be increased during PE (49–51). Since activated platelets occur in some women with PE and are known to produce TGF-β, this would explain why some researchers see an increase in TGF-β during the disease (51).…”

“…Since activated platelets occur in some women with PE and are known to produce TGF-β, this would explain why some researchers see an increase in TGF-β during the disease (51). This could be an explanation for the increase in TGF-β seen in the RUPP rats; however, platelets were not examined in this study, or have they been shown to be increased by others.…”

IFI16 mediates soluble Flt-1 and endoglin production by trophoblast cells

“…It can also significantly affect the fetoplacental unit, causing intrauterine growth restriction and premature birth [3,6,7]. Although the pathophysiologic mechanisms underlying this disease have not yet been fully elucidated, there is evidence that a high level of antiangiogenic molecules, for example, soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng), in the maternal circulation, is associated with this pregnancy complication [8][9][10][11][12].…”