Effects of S1PR2 antagonist on blood pressure and angiogenesis imbalance in preeclampsia rats

Zhang,Tengfei; Guo,Danjie; Zheng,Weiping; Dai,Qunyun

doi:10.3892/mmr.2021.12095

Effects of S1PR2 antagonist on blood pressure and angiogenesis imbalance in preeclampsia rats

Authors:
- Tengfei Zhang
- Danjie Guo
- Weiping Zheng
- Qunyun Dai
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Affiliations: Department of Gynaecology and Obstetrics, Zhuji Affiliated Hospital of Shaoxing University, Zhuji, Zhejiang 311800, P.R. China, Department of Gynecology, Shaoxing People's Hospital and Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, P.R. China, Obstetrics Department, Jinhua Maternal and Child Health Hospital, Jinhua, Zhejiang 321000, P.R. China
Published online on: April 16, 2021 https://doi.org/10.3892/mmr.2021.12095
Article Number: 456

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Abstract

Preeclampsia (PE), a hypertensive multisystem disorder, can lead to increased maternal and fetal mortality and morbidity. Sphingosine‑1‑phosphate (S1P) plays various roles, depending on the cell type, by binding to S1P receptors (S1PR). The present study evaluated the changes of S1PRs and investigated the potential role of S1PRs in pregnancy‑induced hypertension. PE rats were established by reduced uterine perfusion pressure. The involvement of S1PR2 was evaluated using JTE‑013, a specific S1PR2 antagonist, in PE rats. After the treatment, inflammatory cytokines were evaluated using enzyme linked immunosorbent assay, and the expression of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS) activation and endothelial nitric oxide synthase (eNOS) were evaluated by reverse transcription‑quantitative PCR and western blotting. Results showed that S1PR2, but not S1PR1 and S1PR3, was significantly increased in the serum and placenta tissues of PE rats. Notably, JTE‑013 significantly decreased blood pressure, attenuated infiltration of inflammatory cells and decreased inflammation, as indicated by the decreased expression of inflammatory cytokines, including tumor necrosis factor‑α, interleukin‑1β (IL‑1β) and IL‑6, in placental tissues. Mechanistic studies demonstrated that JTE‑013 significantly increased the expression of VEGF and decreased the expression of fms‑like tyrosine kinase 1 in placental tissue. Furthermore, JTE‑013 prevented iNOS activation and increased eNOS in placental tissue. In summary, the present study demonstrated that S1PR2 contributed to hypertension and angiogenesis imbalance in PE rats.

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