783 UPREGULATION OF (PRO)RENIN AND ITS RECEPTOR IN PREECLAMPSIA

Abstract

Objective: Preeclampsia (PreE) is a hypertensive disorder in pregnancy. PreE has multiple pathophysiologic triggers and the renin-angiotensin system (RAS) has been implicated in PreE pathogenesis, however, there is no data showing involvement of (pro)renin and its receptor. Study Design: (1) (Pro)renin levels were assayed in plasma from 32 PreE and 57 NP patients.(2) An established rat model of PreE and normal pregnant (NP) rats were used to evaluate the role of (pro)renin and its receptor in the pathogenesis of PreE. ERK1/2 phosphorylation and plasma and placental levels of RAS components, (pro)renin and its receptor were assayed. (3) Cytotrophoblast (CTB) cells were transfected with human (pro)renin receptor. The binding of (pro)renin to its receptor and the interference of this binding by decoy peptide were assayed. Results: (1) Plasma (pro)renin of PreE patients differs (p < 0.05) from NP. (2) Active renin, renin, and Ang II concentrations in the plasma were lower while placental levels were higher, plasma and placental (pro)renin levels were higher, placental (pro)renin receptor expression and ERK1/2 phosphorylation were higher in PreE compared to NP (p < 0.05). (3) (Pro)renin was activated (85%) by recombinant (pro)renin receptor and the decoy peptide was observed to attenuate this effect. Conclusions: These data suggest that peripheral RAS is downregulated, while uteroplacental RAS is upregulated in PreE. However, both circulatory and uteroplacental (pro)renin and its receptor are upregulated in PreE rats. This study suggests a key role of (pro)renin and its receptor in PreE pathogenesis and involvement of (pro)renin receptor-mediated detrimental cellular signaling in PreE.