Endothelial FOS expression and pre‐eclampsia

Abstract

Objective To study gene expression profiles in human endothelial cells incubated with plasma from women who developed preeclampsia 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 preeclampsia (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 Ò 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 Ò 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 preeclampsia 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.

AP1 mediates uPA/uPAR induced FUT4 expression and trophoblast invasion

“…It has been demonstrated that the expression of both c‐Fos and c‐Jun at the maternal‐fetal interface in rodents and humans, especially those on trophoblast cells, facilitates embryo implantation . The researchers also found that c‐Fos and c‐Jun were decreased in placentas from preeclampsia patients, suggesting that c‐Fos, and c‐Jun are critical for controlling cytotrophoblast function and controlling cytotrophoblast function regulating placental development. In the process of embryo implantation, the decrease in the migration and invasion ability of trophoblasts is the cause of preeclampsia and abortion .…”

Risk factors for perinatal death in two different levels of care: a case–control study

“…These abnormalities result in placental ischemia that leads to release of circulating angiogenic factors that cause preeclampsia. An ischemic intrauterine environment can also lead to intrauterine growth restriction and fetal distress [15]. …”

c‐Fos is involved in inhibition of human bladder carcinoma T24 cells by Brazilin

“…FOS genes are transcription factors, heterodimerize with Jun to form AP‐1 and upregulate great numbers of genes . AP‐1 proteins are primarily considered oncogenic .…”