8C.02: THE SERINE PROTEASE PROSTASIN IS ABERRANTLY FILTRATED IN URINE IN PREECLAMPSIA WITH SIMILAR LEVELS IN PLASMA AND PLACENTA TISSUE COMPARED TO NORMAL PREGNANCY

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Abstract

OBJECTIVE: The serine protease prostasin (PRSS8, CAP1) and its activator matriptase and inhibitor nexin-1 are necessary 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 glomeular barrier.

DESIGN AND METHOD: The hypothesis was addressed in a cross-sectional case-control 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). Prostasin, matriptase, nexin-1 and HAIs were measured by qPCR and western immunoblotting (prostasin, matriptase, nexin-1) and ELISA (prostasin). Aldosterone was measured in plasma and urine by ELISA.

RESULTS: Women with preeclampsia displayed lower levels of aldosterone in plasma 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 placental tissue between groups. Prostasin and nexin protein level in placental homogenate was not different between groups. Active matriptase was expressed at very low levels in placenta. Western blotting showed significantly elevated urine excretion of prostasin in preeclamptic patients compared to controls. Plasma prostasin was not different between groups and did not correlate to aldosterone or placental weight. In summary, preeclampsia is associated with increased urine but not plasma or tissue prostasin

CONCLUSIONS: : It is concluded that placental and plasma prostasin level is not controlled by aldosterone during term pregnancy. In contrast, prostasin is aberrantly filtered and may contribute to renal EnaC activation and suppression of aldosterone in preeclampsia. Potential impact of prostasin-matriptase on placental development is likely to be at the level of activity and not protein abundance.

Original languageEnglish
JournalJournal of Hypertension. Supplement
Volume33 e- Suppl 1
Pages (from-to)e110
ISSN0952-1178
DOIs
Publication statusPublished - Jun 2015

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