Preeclampsia affects 5-7% of all pregnancies and is responsible for more than 7,000 maternal and 500,000 fetal deaths worldwide each year. Preeclampsia is associated with maternal hypertension, vascular injury and kidney and liver dysfunction and can lead to haemolysis, and seizures. It also increases the risk of fetal growth restriction and preterm birth by over 4-fold. A better understanding of the pathophysiology of the disease, and the development of new effective therapies is therefore essential. It is broadly accepted that poor placentation resulting in maternal endothelial and vascular dysfunction causes preeclampsia however, the mechanisms and molecular pathways underlying this pathophysiology are largely unknown.
This presentation will focus on a newly identified molecule, the prorenin receptor (PRR), and its role in both placental development and in causing the clinical symptoms of preeclampsia. We have shown, in a placental specific PRR knockout mice model, that PRR is essential for the establishment of a healthy and functional placenta. We have also demonstrated that high levels of sPRR causes endothelial dysfunction in vitro and that excess maternal circulating sPRR levels cause a preeclampsia-like phenotype (i.e., maternal hypertension and vascular dysfunction) in pregnant rats. Subsequent experiments have demonstrated that blocking the PRR with a specific peptide antagonist, PRO20, can prevent the endothelial dysfunction induced by preeclamptic serum. We therefore propose that not only is soluble PRR the ‘missing link’ in the pathogenesis of preeclampsia, but that targeting soluble PRR is a novel therapeutic strategy to treat this disorder.