Markers and mechanisms of pre-eclampsia in pregnancies complicated by diabetes
type: CreativeWork
description: Pre-eclampsia complicates 2-8% of pregnancies worldwide. Women with diabetes have a 4-fold increased risk of pre-eclampsia compared to the general population. Mechanisms for pre-eclampsia development are not well understood; however, evidence indicates that an increased release of two anti-angiogenic factors, soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng) from placental trophoblasts into the maternal circulation promotes endothelial dysfunction associated with pre-eclampsia. The aim of this thesis was to investigate whether modified lipoproteins and/or elevated glucose have a role in pre-eclampsia in pregnancies complicated by diabetes. Trophoblast cell lines HTR8/SVneo and JAR were exposed to native LDL (N-LDL) vs. ‘highly-oxidized glycated’ LDL (HOG-LDL) (10-200 µg protein/ml) for 24 hours, with and without pre-treatment with 30 mM glucose for 72 hours. The mRNA expressions of sFlt-1 isoforms (sFlt-1-i13, sFlt-1-e15a), endoglin and MMP-14 were measured by RT-PCR, and levels of sFlt-1 and sEng in cell supernatants were determined by ELISA. JAR and BeWo cells were cultured on semi-permeable membrane inserts in Transwell plates for up to 16 days, then exposed to N-LDL vs. HOG-LDL. Transepithelial electrical resistance (TEER) was measured after 6, 12 and 24 hours of treatment and fluorescein-isothiocyanate (FITC)-dextran leakage was measured after 24 hours of treatment. At termination of experiment, tight junction (zonula occludens-1, ZO-1) immunostaining and TUNEL staining were performed. To determine the effects of dysglycaemia and pre-eclampsia on placental pathology, term placentae from two study cohorts were utilized. Pathology in placental sections was examined by performing haematoxylin and eosin (H&E) staining. Immunostaining of Apolipoprotein B100 (ApoB, a marker of LDL), oxidized LDL (Ox-LDL) and 4-hydroxynonenal (4-HNE) was performed. In our in-vitro trophoblast cell model, modified lipoproteins decreased trophoblast cell viability in…
abstract: Pre-eclampsia complicates 2-8% of pregnancies worldwide. Women with diabetes have a 4-fold increased risk of pre-eclampsia compared to the general population. Mechanisms for pre-eclampsia development are not well understood; however, evidence indicates that an increased release of two anti-angiogenic factors, soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng) from placental trophoblasts into the maternal circulation promotes endothelial dysfunction associated with pre-eclampsia. The aim of this thesis was to investigate whether modified lipoproteins and/or elevated glucose have a role in pre-eclampsia in pregnancies complicated by diabetes. Trophoblast cell lines HTR8/SVneo and JAR were exposed to native LDL (N-LDL) vs. ‘highly-oxidized glycated’ LDL (HOG-LDL) (10-200 µg protein/ml) for 24 hours, with and without pre-treatment with 30 mM glucose for 72 hours. The mRNA expressions of sFlt-1 isoforms (sFlt-1-i13, sFlt-1-e15a), endoglin and MMP-14 were measured by RT-PCR, and levels of sFlt-1 and sEng in cell supernatants were determined by ELISA. JAR and BeWo cells were cultured on semi-permeable membrane inserts in Transwell plates for up to 16 days, then exposed to N-LDL vs. HOG-LDL. Transepithelial electrical resistance (TEER) was measured after 6, 12 and 24 hours of treatment and fluorescein-isothiocyanate (FITC)-dextran leakage was measured after 24 hours of treatment. At termination of experiment, tight junction (zonula occludens-1, ZO-1) immunostaining and TUNEL staining were performed. To determine the effects of dysglycaemia and pre-eclampsia on placental pathology, term placentae from two study cohorts were utilized. Pathology in placental sections was examined by performing haematoxylin and eosin (H&E) staining. Immunostaining of Apolipoprotein B100 (ApoB, a marker of LDL), oxidized LDL (Ox-LDL) and 4-hydroxynonenal (4-HNE) was performed. In our in-vitro trophoblast cell model, modified lipoproteins decreased trophoblast cell viability in…
author: McLeese, Rebecca
language: eng
keywords: Pre-eclampsia, diabetes, modified lipoproteins, pregnancy
date published: 2019-7
date modified: 2026-07-24T03:55:51Z
provider: Queen's University Belfast
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queen's University Belfast