Key result
Preeclampsia was associated with a significantly lower activated (pro)renin concentration in the second trimester (599.4 pg/ml vs 994.8 pg/ml, p<0.01) compared to normal pregnancies, alongside increased placental (P)RR expression.
Why the study?
Although an association between preeclampsia and (pro)renin was reported, the involvement of (pro)renin via intracellular signaling of the (pro)renin receptor in the pathogenesis of preeclampsia remained to be clarified.
Does (pro)renin receptor signaling contribute to the pathogenesis of preeclampsia via ET-1 production?
Case-Control (n=43)
No
Does (pro)renin receptor signaling contribute to the pathogenesis of preeclampsia via ET-1 production?
Absolute Event Rate: 599.4% vs 994.8%
p-value: p=<0.01
Intracellular signaling of the (pro)renin receptor in the placenta under hypoxic conditions increases ET-1 production, suggesting a potential mechanism for the development of hypertension in preeclampsia.
Preeclampsia-linked lower activated (pro)renin should not change practice; hypothesis-generating for placental (P)RR in pathogenesis.
An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia.
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Tamada et al. (2019) conducted a case-control in Preeclampsia (n=43). Preeclampsia vs. Normal pregnancy was evaluated on Activated (pro)renin concentration in the second trimester (p=<0.01). Preeclampsia was associated with a significantly lower activated (pro)renin concentration in the second trimester (599.4 pg/ml vs 994.8 pg/ml, p<0.01) compared to normal pregnancies, alongside increased placental (P)RR expression.
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