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Previous issue date: 2014-02-24 / 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 protein?ria. 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 S?o 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. / A pr?-ecl?mpsia ? uma das principais causas de mortalidade materna no mundo. Embora alguns fatores etiol?gicos, tais como m? placenta??o, disfun??o endotelial, inflama??o materna exacerbada, angiog?nese deficiente e hipoxia placent?ria t?m sido propostos, a etiologia da pr?-ecl?mpsia ainda n?o foi completamente compreendida. A teoria da m? adapta??o imune sugere que a pr?-ecl?mpsia pode estar envolvida com um desbalan?o Th1/Th2 prejudicial ? gesta??o, com libera??o de citocinas e fatores de crescimento na circula??o materna. A presen?a desses mediadores parece desempenhar um papel na fisiopatologia da pr?-ecl?mpsia, resultando nos sinais cl?nicos da doen?a: a hipertens?o e a protein?ria. Assim, este estudo pretendeu analisar diferentes vias metab?licas durante a gesta??o, a fim de tentar elucidar um biomarcar para a doen?a. Nossa hip?tese ? a de que mol?culas relacionadas ao sistema inflamat?rio estariam aumentadas no plasma materno e na placenta de mulheres com pr?-eclampsia e diminu?das no plasma fetal. O estudo foi realizado no Hospital S?o Lucas da PUCRS, Brasil, onde fizemos a coleta das amostras para o projeto Mol?culas mediadoras e a pr?-ecl?mpsia, e no St Thomas Hospital, em Londres, Reino Unido, onde os projetos Lipoprote?nas e a pr?-eclampsia e Prote?nas das cav?olas e a pr?-ecl?mpsia foram desenvolvidos. No HSL/PUCRS, amostras de plasma materno-fetal e placenta foram coletadas de 117 gestantes com e sem pr?-ecl?mpsia no terceiro trimestre da gesta??o. As mol?culas (Endocan-1, PIGF, IL-6, TNFα, MCP-1, NGF, LIGHT e Leptina) foram dosadas por ensaio de detec??o multiplex. Em Londres, um estudo com 51 gestantes foi realizado analisando express?o placent?ria das seguintes mol?culas: receptores e mediadores de lipoprote?nas (LRP-1, LDL-R, SRB1, ABCA1, MTTP e PDIA2) e prote?nas do complexo das cav?olas (Caviolina-1-3, Cavins 1-4, eNOS e iNOS ), que foram analisadas por PCR-TR e imuno-histoqu?mica. Resumidamente, encontramos altos n?veis de Endocan-1 e TNFα no plasma materno, baixos n?veis de IL-6 no plasma fetal de pacientes com pr?-eclampsia, no ensaio de citocinas. Ainda, foi encontrada uma correla??o entre o gene LRP-1 e rec?m-nascidos pequenos para a idade gestacional, no grupo com pr?-ecl?mpsia, no ensaio de receptor de lipoprote?nas. E, por fim, uma redu??o da express?o de Caveolina-1 na placenta pr?-ecl?mptica foi observada e parece ter resultado numa ativa??o compensat?ria cr?nica da eNOS para tentar atenuar a vasoconstri??o observada na pr?-eclampsia. Concluindo, nossos resultados mostraram novos dados em rela??o ? pr?-ecl?mpsia, que podem ser ?teis para o entendimento de sua fisiopatologia.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/1764 |
| Date | 24 February 2014 |
| Creators | Hentschke, Marta Ribeiro |
| Contributors | Figueiredo, Carlos Eduardo Poli de |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de, PUCRS, BR, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7620745074616285884, 500, 600, -8624664729441623247 |
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