Prostasin, proteases, and preeclampsia.

P reeclampsia is a leading cause of perinatal morbidity and mortality, affecting between 5 and 8% of pregnancies worldwide [1]. The syndrome is characterized by development of hypertension (SBP 140 mmHg and/or DBP 90mmHg) and proteinuria ( 300 mg/24 h or 2þ on urine dipstick testing) after the 20th gestational week and its rising incidence is partially attributed to the increased prevalence of predisposing conditions such as diabetes and obesity. Preeclampsia is associated with multiple potentially fatal short-term complications, including preterm delivery, hepatic or renal dysfunction, seizures, and coagulopathy, and is responsible for up to 15% of maternal deaths worldwide [2]. In addition, the diagnosis carries important implications for maternal health in the longer term with greater risk of cardiovascular and renal disease in later life [3]. Although the consequences for mother and infant can be disastrous early disease detection and treatment options remain very limited, partially as a result of our incomplete understanding of the interplay between the many complex pathophysiological mechanisms underlying the condition. The fact that the condition resolves with delivery of the placenta highlights the critical role of the organ in the development of preeclampsia, and abnormal cytotrophoblast invasion coupled with failure of spiral artery remodelling in early gestation are thought to be a key component of the disease process [4]. This abnormal placentation is driven, at least in part, by an imbalance of pro and antiangiogenic factors; in particular soluble vascular endothelial growth factor (VEGF) receptor 1 (soluble fmsrelated tyrosine kinase 1; sFlt-1) and placental growth factor (PlGF). A large body of evidence demonstrates elevated sFlt-1 availability in preeclamptic pregnancies prior to the onset of the clinical syndrome, with a resultant inhibitory effect on VEGF and PlGF signalling [5]. In fact, the ratio of sFlt-1 : PlGF at 34 weeks gestation has been shown to

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