title: Endothelial FOS expression and pre-eclampsia.
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.
  
  
  METHODS
  A case-control study.
  
  
  METHODS
  A longitudinal nested case-control study within three maternity units.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Mackenzie
authors.forename: V C
authors.initials: VC
authors.lastname: Sandrim
authors.forename: D M
authors.initials: DM
authors.lastname: Carty
authors.forename: J D
authors.initials: JD
authors.lastname: McClure
authors.forename: D J
authors.initials: DJ
authors.lastname: Freeman
authors.forename: A F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: M W
authors.initials: MW
authors.lastname: McBride
authors.forename: C
authors.initials: C
authors.lastname: Delles
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016762:Genes, fos; D005819:Genetic Markers; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008137:Longitudinal Studies; D020411:Oligonucleotide Array Sequence Analysis; D010949:Plasma; D011225:Pre-Eclampsia / Q000097:blood / Q000235:genetics*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D005819:Genetic Markers