M14.2 Novel splice variants of Flt1 are upregulated in the placenta in severe early onset pre-eclampsia

Abstract

Background: Alternative splicing of fms –like tyrosine kinase 1 (Flt-1) produces a soluble protein (sFlt v1), which is markedly increased in the blood of pre-eclamptic women. It is believed that this angiogenic factor plays an important role in the pathogenesis of pre-eclampsia. A novel splice variant (sFlt_v2) has recently been discovered and may be elevated in pre-eclampsia. Preliminary reports suggest that, like pre-eclampsia, the novel variant may be specific to human and primate placentae. It has not as yet been characterised in severe early onset pre-eclampsia. Aims: To determine expression of the sFlt_v2 in the placenta in severe early onset pre-eclampsia Methods: Placenta was collected at delivery from 16 pre-eclamptic women (gestational age range 22-34 weeks), six pre-eclamptics complicated by HELLP syndrome (range 24 – 36 weeks), 15 normotensive women with spontaneous preterm labour (range 28-36 weeks) and 30 term normotensive controls (range 38-42 weeks). RNA was isolated from the placental tissue and transcribed into cDNA. Real-Time qPCR was performed for Flt1, sFlt_v1 and sFlt_v2 and expression levels were normalized to the housekeeping gene. Results: The expression of sFlt_v1 and sFlt_v2, and Flt1, were increased in placentae in severe pre-eclampsia compared to normotensive controls. sFlt_v2 was the predominant variant expressed in the placenta in severe early onset pre-eclampsia. Conclusions: The recently discovered sFlt variant (sFlt_v2) is the predominant splice variant expressed in the placenta in severe early onset pre-eclampsia. This discovery may have important implications on improving our understanding of pre-eclampsia, its diagnosis and in the development of potential therapeutics.