Role of Elevated SFLT‐1 on the Regulation of Placental Transporters in Women With Pre‐Eclampsia
Dea Kojovic, Natalie V. Workewych, Micheline Piquette‐Miller
Abstract
Pre-eclampsia (PE) is an obstetric complication associated with elevated levels of fms-like tyrosine kinase 1 (sFlt-1) and dysregulated trophoblast differentiation. However, limited information exists on the expression and regulation of placental drug transporters in PE. Transporter mRNA and protein expression were analyzed in human placentas diagnosed with PE (n = 34) and gestational age-matched controls (n = 24), whereas placental BeWo cells were treated with angiogenic factors in vitro. Significant downregulation of breast cancer resistance protein (BCRP) and several other transporters were seen in placentas complicated by PE compared with controls, whereas mRNA levels of sFlt-1 were induced by 2.5-fold in PE placentas (P < 0.01). Treatment of BeWo cells with sFlt-1 resulted in an 85-90% downregulation of BCRP, which was attenuated by vascular endothelial growth factor. Our findings suggest that placental function is compromised during PE due to altered expression of clinically important transporters. Furthermore, our in vitro results show that sFlt-1 is involved in the regulation of BCRP.