The Expression of Placental Proteoglycans in Pre-Eclampsia

C1 - Journal Articles RefereedBACKGROUND/AIMS: Pre-eclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality. PE is defined clinically as the onset of maternal hypertension and proteinuria following 20 weeks of gestation. It is associated with altered maternal uterine decidual spiral artery remodelling, which may lead to reduced blood flow and increased thrombosis within the uteroplacental vasculature. Proteoglycans (PGs) are macromolecules which have (in combination with glycosaminoglycans) important anticoagulant roles in vascular endothelial environments, including the uteroplacental circulation. The hypothesis under consideration in this study was that differential expression of placental PGs may be associated with PE. METHODS: PE and control placental samples were collected with ethics approval and patient consent. RNA and protein were extracted and real-time PCR and Western immunoblotting were performed to determine the expression of the PGs in the samples. RESULTS: Of the nine PGs investigated, none showed increased expression, whereas the mRNA and protein expression of five of them was significantly decreased in the placentae of pre-eclamptic women compared to gestation-matched controls. CONCLUSION: Therefore, the results of this study support the hypothesis that a placental PG deficiency may contribute to the placental thrombotic lesions characteristic of PE

Altered decorin leads to disrupted endothelial cell function: A possible mechanism in the pathogenesis of fetal growth restriction?

The fulltext of this publication will be made publicly available after relevant embargo periods have lapsed and associated copyright clearances obtained.Full text embargoed until: 2015-08-31OBJECTIVE: Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae. APPROACH: Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed. RESULTS: DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies. CONCLUSIONS: Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations

Methylmalonic acid values in healthy Dutch children.

Contains fulltext : 69271.pdf (publisher's version ) (Closed access)BACKGROUND: Plasma methylmalonic acid (MMA) is a specific marker for functional cobalamin deficiency. This deficiency can give rise to non-specific but serious symptoms in childhood such as developmental delay, convulsions and failure to thrive and may even lead to irreversible neurological damage. AIM OF THE STUDY: To analyse plasma MMA concentrations in Dutch children and to evaluate possible factors influencing its concentration. METHODS: A number of 186 Dutch children aged 0-19 years were analysed cross-sectionally. Blood was collected to measure MMA, total homocysteine (tHcy), cobalamin (Cbl) and serum creatinine concentrations. In addition, information about medical history, age and sex was recorded. RESULTS: The geometric mean (GM) plasma MMA concentration was 0.17 micromol/l (95% CI 0.07-0.42) and the GM tHcy was 6.6 micromol/l (95% CI 3.1-13.9). There is a slight positive correlation between plasma MMA and age in children >1 year (r = 0.211, P < 0.05). Plasma MMA concentrations were significantly higher in children with low Cbl concentrations. No significant difference in MMA, Cbl, tHcy or creatinine concentrations between sexes could be observed. Regression analysis showed that Cbl was the strongest determinant of plasma MMA (regression coefficient -0.414, P < 0.05). The association between MMA and Cbl is stronger at increasing age (P for trend 0.045). CONCLUSIONS: Plasma Cbl is the main determinant of MMA in this group of Dutch children. The strength of the association increased with increasing age