Abstract 314: Elevation of (pro)renin and Its Receptor in Preeclampsia: A Rat Model and Human Patients
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Preeclampsia (PreE), a syndrome manifesting with hypertension, proteinuria, and edema, is a leading cause of maternal and fetal morbidity and mortality. While preE triggers are likely many and elusive, the renin-angiotensin system (RAS) has been implicated in preE pathogenesis. However, there is no data showing involvement of (pro)renin and its receptor. We recruited 32 preE and 57 normal pregnant consenting patients. (Pro)renin levels were assayed in plasma samples using an ELISA kit. An established rat model of preE was used to evaluate the role of (pro)renin and its receptor in pathogenesis. We used normal pregnant rats (NP, n=10) and pregnant rats receiving weekly injections of desoxycorticosterone acetate and whose drinking water was replaced with 0.9% saline (PreE, n=10). The plasma and placental levels of (pro)renin were assayed by ELISA. The placental levels of (pro)renin receptor was measured by gel electrophoresis of the placental homogenate followed by detection with immunoblotting using anti-ATP6IP2 antibody. The ERK1/2 phosphorylation was analyzed by immunoblotting using antibodies to total and active ERK1/ERK2 in the placenta. The mean plasma (pro)renin of 0.27 0.04 g/mL in preE patients differ (p < 0.001 using Students t test) from 0.15 0.05 g/mL in those without preE. Both plasma and placental levels of (pro)renin were higher (p < 0.001 using Kolmogorov-Smirnov test) in PreE rats compared to NP (Plasma (pro)renin for NP:0.21 0.04 and PreE:0.49 0.09 pg/mL; placental (pro)renin for NP:152 79 and PreE:302 42 ng/g tissue). In addition to serving as a source of (pro)renin, the placenta is also a site for signaling as ERK1/2 phosphorylation is greater (p<0.05) in placental tissue of preE rats. These data show that circulatory and uteroplacental (pro)renin and its receptor are upregulated. Together with the upregulation of ERK1/2 phosphorylation in placenta of the rat model, there is now evidence of (pro)renin and its receptor associated novel RAS activation to play a role in preE pathogenesis through (pro)renin receptor-mediated detrimental cellular signaling at the placental boundary. This offers an opportunity for interventional treatments with signal inhibitors and interference with nonclassical (pro)renin activation of RAS.
