[280-POS]: Prostasin and its regulatory proteins in human placentas from pregnant women with preeclampsia and healthy pregnant controls.

OBJECTIVES: Serine proteases are enzymes involved in digestion, immune response, blood coagulation and reproduction. The serine protease prostasin (PRSS8, CAP1) and its regulatory associated proteins (Matriptase, Hepatocyt growth factor activator inhibitors (HAIs), and Nexin-1) are essential for normal placental development in mice. Prostasin is regulated by aldosterone in the kidney and may activate the epithelial sodium channel (ENaC). Preeclampsia is characterized by disturbed placentation, suppression of aldosterone and avid renal sodium retention with hypertension. It was hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier.

METHODS: This hypothesis was addressed in a cross-sectional design with 20 healthy pregnant women and 20 women with new onset of preeclampsia (hypertension and 1+ for protein on urine dipstick). Blood and urine samples were obtained in relation to delivery and placental biopsies were taken immediately after delivery (control = 39 and preeclampsia 40 weeks).

RESULTS: Women with preeclampsia displayed lower levels of aldosterone in plasma (p=0.0475) and in spot urine normalized for creatinine (p=0.0001). Placental weight was not different between groups. Prostasin, matriptase, HAI 1 and 2, and nexin mRNA abundances were not different in placenta tissue between groups. Prostasin protein level in placental homogenate was not different between groups as judged from western blotting and ELISA assay. Western blotting showed significantly elevated urine excretion of prostasin in preeclamptic patients compared to controls. Plasma aldosterone correlated directly with placental weight (p=0.022), while plasma prostasin did not correlate to aldosterone or placental weight. No correlation between aldosterone and systolic or diastolic blood pressure was found.

CONCLUSIONS: It is concluded that altered prostasin activity in placenta in preeclampsia is likely to be at the level of activity and not protein abundance. In perspective, urine prostasin may contribute to renal EnaC activation.

DISCLOSURES: B. Frederiksen-Møller: None. J.S. Jørgensen: None. L.K. Vogel: None. B.L. Jensen: None.