Endothelial FOS expression and pre-eclampsia

MacKenzie, R.M., Sandrim, V.C., Carty, D.M., McClure, J.D. , Freeman, D.J. , Dominiczak, A.F. , McBride, M.W. and Delles, C. (2012) Endothelial FOS expression and pre-eclampsia. BJOG: An International Journal of Obstetrics and Gynaecology, 119(13), pp. 1564-1571. (doi: 10.1111/1471-0528.12016)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McBride, Dr Martin and Freeman, Dr Dilys and Dominiczak, Professor Anna and Delles, Professor Christian and MacKenzie, Dr Ruth and Carty, Dr David and McClure, Dr John
Authors: MacKenzie, R.M., Sandrim, V.C., Carty, D.M., McClure, J.D., Freeman, D.J., Dominiczak, A.F., McBride, M.W., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:BJOG: An International Journal of Obstetrics and Gynaecology
Publisher:Wiley-Blackwell Publishing Ltd.
Published Online:02 November 2012

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
515251EuratransAnna DominiczakEuropean Commission (EC)241504RI CARDIOVASCULAR & MEDICAL SCIENCES
482901Assessment of endothelial function in pregnancy: evaluation of a non-invasive method to analyse flow-mediated vasodilationChristian DellesNHS Greater Glasgow & Clyde West Research Endowment Fund (NHGGC-WEND)07REF003W DelleRI CARDIOVASCULAR & MEDICAL SCIENCES