Yang Yuelai, Jiang Lei, Chang Ruijing, Liu Jing, Xin Hong, Ji Wanli
Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.
Department of Obstetrics, The Second Hospital of Hebei Medical University, Shijiazhuang, 050004, China.
Reprod Sci. 2024 Dec;31(12):3825-3833. doi: 10.1007/s43032-024-01668-8. Epub 2024 Aug 12.
Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.
子痫前期（PE）是妊娠期一种与高血压相关的特定疾病，可导致不良妊娠结局。内皮细胞功能障碍是PE的主要病因，其调节可能影响疾病进展。本研究聚焦于hsa_circ_0088196，评估其在PE中的临床意义及其对内皮细胞损伤的影响，旨在确定一种新的PE生物标志物并完善其在疾病发展中的调控机制。该研究纳入了165例正常妊娠和165例妊娠期高血压妊娠。基于血清表达评估hsa_circ_0088196在鉴别妊娠期高血压、预测PE以及预测不良妊娠结局方面的意义。通过CCK8、Transwell、ELISA和蛋白质印迹法评估hsa_circ_0088196在人脐静脉内皮细胞（HUVEC）损伤中的作用及机制。hsa_circ_0088196的显著下调可区分妊娠期高血压妊娠并预测PE风险。发生PE的妊娠期高血压妊娠血清hsa_circ_0088196水平较低，这也可鉴别PE患者、预测严重病情及不良妊娠结局。过表达hsa_circ_0088196可减轻缺氧/复氧（H/R）诱导的增殖、迁移、炎症和血管生成增强，而这一作用被miR-145-5p逆转。沉默miR-145-5p对H/R诱导的内皮细胞损伤显示出类似作用，而这一作用被Fms样酪氨酸激酶1（FLT1）逆转。此外，hsa_circ_0088196对FLT1有正向调控作用，表明其参与hsa_circ_0088196对HUVEC损伤的调控。血清hsa_circ_0088196降低可作为诊断妊娠期高血压、评估PE风险及预测不良妊娠结局的生物标志物。hsa_circ_0088196通过调节miR-145-5p/FLT1轴抑制H/R诱导的内皮细胞损伤。
