Pré-eclampsia: avaliação de endoglina solúvel, fator de crescimento transformante beta 1 e receptores solúveis do fator de necrose tumoral alfa

Abstract

Preeclampsia (PE) is characterized by the onset of hypertension and proteinuria in normotensive pregnant women after the twentieth week of gestation. Clinically, it is important to diagnose the severe form of PE, in which the systemic involvement is higher. According to the gestational age at PE onset, this disease can also be classified in early PE or late PE (<34 or 34 weeks of gestation). Studies suggest that an imbalance between angiogenic factors, such as soluble endoglin (sEng) and transforming growth factor beta-1 (TGF-â1), as well as an exacerbated inflammatory state, contribute to the endothelial dysfunction and the clinical manifestations of the disease. The main objective of this study was to evaluate the association between plasma levels of sEng, TGF-â1 and TNF-á soluble receptors (sTNF-R1 and sTNF-R2) and the occurrence of PE, classified according to the severity and onset-time of the disease. We evaluated 87 women: 23 non pregnant, 21 normotensive pregnant and 43 preeclamptic. Pregnant women with PE were stratified into subgroups according to the severity [mild PE (n=12) and severe PE (n=31)] and onset-time of the disease [early PE (n=19) and late PE (n=24)]. Plasma levels of sEng TGF-â1, sTNF-R1 and sTNF-R2 were determined by ELISA. The results showed that sEng and sTNF-R1 levels were higher in preeclamptic than in normotensive pregnant (sEng: p<0.001, sTNF-R1: p=0.014) and non-pregnant (all p<0.001), and in normotensive pregnant compared with non-pregnant (all p<0.001). sTNF-R2 levels were higher in preeclamptic compared with non-pregnant (p<0.001), but no difference was found comparing with normotensive pregnant women. The same parameter was increased in normotensive pregnant compared with non pregnant women (p<0.001). No differences were found in TGF-â1 levels between the three studied groups. Late PE had higher levels of sTNF-R1 (p=0.004) and sTNF-R2 (p=0.003) than early PE and no significant difference was found for sEng and TGF-â1 levels. sEng levels were higher in severe PE comparing to mild PE (p=0.005) and no difference was found for TGF-â1, sTNF-R1 and sTNF-R2 levels. Logistic regression analysis revealed that primiparity and sEng plasma levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity. No variable analyzed was independently associated with onset-time of the disease. These results suggest that sEng, sTNF-R1 and sTNF-R2 are associated with pregnancy, and that sEng and sTNF-R1 are higher in preeclamptic women. In addition, these data suggest that elevated levels of both TNF-á receptors are associated with late PE, while higher levels of sEng are found in pregnant women with severe PE.