The pathogenesis of pre-eclampsia is thought to involve a two-stage process. The first stage is characterised by defective placental angiogenesis. Abnormal placentation and failure in the remodelling of spiral arteries leads to the secretion of placental factors into the maternal circulation in the second stage, and to widespread systemic effects in the mother.1 Among the factors released by the placenta are cytokines, bioactive cellular debris from the trophoblast and a variety of anti-angiogenic factors, including soluble endoglin (sEng) and the soluble form of the vascular endothelial growth factor (VEGF) receptor (soluble FMS-like tyrosine kinase-1, Flt-1).1 VEGF regulates gene transcription via transcription factors such as FOS. The FOS gene family consists of four members that encode leucine zipper proteins: FOS, FOSB, FOSL1 and FOSL2. They dimerise with proteins of the JUN family to form the transcription factor complex AP-1. The c-Fos proto-oncogene is a transcription factor encoded by the FOS gene, and has been implicated as a regulator of cell proliferation, differentiation and transformation.2,3
One of the hallmarks of pre-eclampsia is systemic maternal endothelial dysfunction.4Ex vivo myography studies in subcutaneous resistance arteries demonstrated that normal pregnancy is associated with a marked improvement in endothelium-dependent vasodilation, whereas vessels from women with pre-eclampsia are characterised by an impaired response to vasodilatory stimuli.5,6 Endothelial dysfunction in pre-eclampsia has been confirmed in clinical studies using ultrasound-derived flow-mediated vasodilation.7,8 In women in whom pre-eclampsia develops, impaired endothelium-dependent vasodilation, as assessed by skin microvascular function using iontophoresis of acetylcholine, has also been shown to precede the development of the clinical syndrome.9
Plasma of women in which pre-eclampsia develops has been found to cause impaired endothelium-dependent vasodilatation in in vitro studies.10 Other studies highlight a role of microparticles in the maternal plasma of women with pre-eclampsia, causing endothelial dysfunction.11 Some of the effects of plasma from women with pre-eclampsia on endothelial cells are the result of the activation of monocytes and subsequent inflammatory responses.12,13 A previous study by Donker et al.14, using microarray technology, investigated the effects of the plasma factors present in severe early-onset pre-eclampsia on gene expression profiles in human umbilical vein endothelial cells (HUVECs). This study failed to detect substantially altered endothelial gene expression on exposure to pre-eclamptic plasma factors.
We aimed to improve upon previous investigations by using HUVECs from a single donor and plasma obtained at both early (16 weeks of gestation) and mid pregnancy (28 weeks of gestation). We investigated whether plasma contains soluble factors that have effects on gene expression in endothelial cells. Our study was not, however, designed to identify factors that lead to impaired placentation.