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- W2898780391 abstract "Objectives: Elevated soluble (pro)renin receptor [s(P)RR] concentration in maternal blood is associated with gestational hypertension and preeclampsia. Placental ischemia is a presumed trigger of gestational hypertension, and because placenta has abundant expression of (P)RR, the binding of which with pyruvate dehydrogenase E1 beta subunit (PDHB) is recently reported to maintain oxidative metabolism, we hypothesized that placental (P)RR may be induced by hypoxia and have a role in the pathogenesis or maintenance of hypertensive disorders of pregnancy. Methods: Expression and functional analyses were performed using human trophoblast cells, JAR and JEG3. Results: Endogenous expression of (P)RR and PDHB were confirmed in two trophoblast cell lines, and (P)RR showed co-immunoprecipitation and co-immunofluorescence with PDHB mainly in mitochondria. Subjecting the cells to hypoxia in a chamber system increased s(P)RR protein expression by 4.3 ± 0.4 fold (1% O2 for 8 hours, N = 6, P < 0.05). While hypoxia reduces PDH activity in several non-trophoblast cell lines, hypoxia treatment did not alter PDHB expression or PDHB activity in trophoblasts; however, knockdown of (P)RR by siRNA in trophoblasts significantly reduced PDHB protein expression and PDH activity under hypoxia. Acetyl-CoA, the product of PDH activity, was also significantly reduced by (P)RR siRNA under hypoxia. Conclusion: Induction of s(P)RR in trophoblasts may serve to maintain oxidative metabolism and efficient energy production during hypoxia. While increased serum s(P)RR concentration in maternal blood may reflect placental ischemia, whether elevated s(P)RR leads to deleterious effects on the mother such as by activating systemic renin angiotensin system remains to be determined." @default.
- W2898780391 created "2018-11-09" @default.
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- W2898780391 date "2018-10-01" @default.
- W2898780391 modified "2023-09-25" @default.
- W2898780391 title "A6066 Induction of (pro)renin receptor by hypoxia in trophoblasts and its possible role in hypertensive disorders of pregnancy" @default.
- W2898780391 doi "https://doi.org/10.1097/01.hjh.0000548168.13553.e9" @default.
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