ABSTRACT
OBJECTIVE: To study gene expression profiles in human endothelial cells incubated with plasma from women who developed pre-eclampsia and women with normotensive pregnancies. DESIGN: A case-control study. SETTING: A longitudinal nested case-control study within three maternity units. POPULATION: A mixed obstetric population attending maternity hospitals in Glasgow. METHODS: Plasma was obtained at both 16 and 28 weeks of gestation from 12 women: six women subsequently developed pre-eclampsia (cases) and six women, matched for age, body mass index (BMI) and parity, remained normotensive (controls). Human umbilical vein endothelial cells (HUVECs) were incubated with plasma for 24 hour before RNA isolation. MAIN OUTCOME MEASURES: Gene expression profiles were compared between the two gestational time points using Illumina(®) HumanHT-12 v4 Expression BeadChips. Differential mRNA expression observed in microarray experiments were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and gene networks were analysed using Ingenuity(®) pathway analysis. RESULTS: There was a significant difference in the expression of 25 genes following incubation with plasma from controls, and an increase in the expression of 11 genes following incubation with plasma from cases, with no overlap between the two groups (false discovery rate, FDR < 0.05). There was a 3.74-fold (FDR < 0.001) increase in the expression of the c-Fos gene (FOS) when HUVECs were incubated with control plasma from 16 and 28 weeks of gestation, with no significant difference between the two time points with plasma from cases. Similar findings for FOS were obtained by qRT-PCR. CONCLUSIONS: Plasma from women who subsequently develop pre-eclampsia appears to contain factors that lead to the dysregulation of FOS in endothelial cells during pregnancy. Reduced expression of c-Fos may lead to impaired vasculogenesis, and thereby contribute to the development of pre-eclampsia.
Subject(s)
Gene Expression Regulation , Genes, fos , Human Umbilical Vein Endothelial Cells , Pre-Eclampsia/genetics , Transcriptome , Case-Control Studies , Cells, Cultured , Female , Gene Expression Profiling , Gene Regulatory Networks , Genetic Markers , Humans , Longitudinal Studies , Oligonucleotide Array Sequence Analysis , Plasma , Pre-Eclampsia/blood , Pregnancy , Pregnancy Trimester, Second , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
If bone mineral density (BMD) screening is to achieve the aim of preventing the complications of osteoporosis, women with low BMD measurements must learn that they are at risk, and women at risk must know about and be willing to adopt and persist with measures that can prevent osteoporosis. In this paper we present the results of a randomized controlled trial designed to examine whether disclosing the results of a BMD scan directly to women, as well as through their general practitioners (GPs), improves their knowledge of their bone density results without adverse psychological sequelae. Direct disclosure resulted in 19% (59% vs 40%; 95% CI for difference in proportions: 9.8% to 27.8%) more women being aware of their BMD status at the spine and 22% (58% vs 36%; 95% CI for difference: 12.2% to 29.8%) at the hip. These differences were observed irrespective of risk status. There was no significant difference in anxiety levels between the randomized groups. We conclude, therefore, that direct disclosure of BMD results to women, as well as to their GPs, leads to increased knowledge of BMD status without increasing anxiety, and that BMD measurement services should consider informing women routinely of their results directly as well as through their GPs.
