Open AccessEffects of S1PR2 antagonist on blood pressure and angiogenesis imbalance in preeclampsia rats
Author(s) -
Tengfei Zhang,
Danjie Guo,
Wenjie Zheng,
Qunyun Dai
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12095
Subject(s) - endocrinology , medicine , enos , s1pr1 , angiogenesis , nitric oxide synthase , preeclampsia , vascular endothelial growth factor , nitric oxide , tumor necrosis factor alpha , biology , trophoblast , placenta , vascular endothelial growth factor a , fetus , pregnancy , genetics , vegf receptors
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.