Endothelial FOS expression and pre-eclampsia

Authors


Dr C Delles, Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK. Email christian.delles@glasgow.ac.uk

Abstract

Please cite this paper as: Mackenzie RM, Sandrim VC, Carty DM, McClure JD, Freeman DJ, Dominiczak AF, McBride MW, Delles C. Endothelial FOS expression and pre-eclampsia. BJOG 2012;119:1564–1571.

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.

Ancillary