Pré-eclâmpsia : avaliação de aspectos fisiopatológicos e clínicos

Abstract

Pre-eclampsia is one of the leading cause of maternal mortality worldwide. Although some etiological factors such as poor placentation, endothelial dysfunction, excessive maternal inflammation, poor angiogenesis, and placental hypoxia have been proposed, the etiology of pre-eclampsia has not been fully understood. An immune maladaptation theory suggests that pre-eclampsia might be envolved in an inappropriate regulation of normally Th2-deviated maternal immune response, leading to a shift toward harmful Th1 immunity, delivering a large amount of cytokines and growth factor molecues throw maternal circulation. The presence of these mediators seems to play a role in the pathophysiology of pre-eclampsia, resulting in the clinical signs of the disease: hypertension and proteinúria. Thus, this study pretended to analize different pathways during gestation in order to try to elucidate a biomarcar for the disease. We hypothesize that moleculas related to inflammatory system would be up-regulated in maternal plasma and placenta from women with pre-eclampisa and down regulated in fetal plasma. The study was performed at Hospital São Lucas of PUCRS, Brazil, where we made Mediating molecules and pre-eclampsia , and at St Thomas‟ Hospital, London, UK, where Lipoproteins and pre-eclampsia and Caveola proteins and pre-eclampsia projects were developed. At HSL/PUCRS, maternal/fetal plasma and placenta samples were collected from 117 pre-eclampsia and normal pregnant women in third trimester pregnancy, after informed written consent. The cytokines (Endocan-1, PlGF, IL-6, TNFα, MCP-1, NGF, LIGHT, Leptina) were measured by multiplex detecting assay. In London, a study with 51 pregnant women was conducted analising placenta expression of the following molecules: lipoproteins pathway (LRP-1, LDL-R, SRB1, ABCA1, MTTP and PDIA2) and protein caveolae complex (Caveolin-1-3, cavins 1-4, eNOS and iNOS) which were performed by PCR-RT e immunohistochemistry. Briefly we found high levels of Endocan-1 and TNFα in pre-eclamptic maternal plasma, low levels of IL-6 in fetal plasma in cytokines assay. Also a correlation between LRP-1 gene and small for gestational age infants in lipoproteins receptor assay was found. Finally, a reduction expression of Caveolin-1 found in pre-eclampstic placenta seems to result in a compensatory chronic activation of eNOS to attenuate vasoconstriction seen in pre-eclampsia. In conclusion, our results showed new data in relation to pre-eclampsia, which might be helpful for the understanding of its pathofisiology.