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Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Plasma Exosomal miR-199a-5p Derived from Preeclampsia with Severe Features Impairs Endothelial Cell Function via
Zhirui Chen1,2, Mengying Wu2, Haixia Huang2
1Department of Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Insights
Upregulated exosomal miR-199a-5p in severe preeclampsia (sPE) impairs endothelial cell function by targeting SIRT1. This suggests a novel mechanism contributing to sPE development under oxidative stress.
Area of Science:
- Obstetrics and Gynecology
- Molecular Biology
- Cell Biology
Background:
- Preeclampsia (PE) is a serious pregnancy complication with significant maternal and fetal risks.
- Plasma exosomes increase during pregnancy, indicating their role in pregnancy development.
- Previous research implicated exosomal miR-199a-5p in severe preeclampsia (sPE).
Purpose of the Study:
- To elucidate the role of exosomal miR-199a-5p in the pathogenesis of sPE.
- To investigate the regulatory mechanisms and cellular effects of exosomal miR-199a-5p in sPE.
Main Methods:
- Quantification of miR-199a-5p in plasma exosomes and placental tissue from sPE patients and normal controls.
- In vitro studies using BeWo cells and human umbilical venous endothelial cells (HUVECs) to assess miR-199a-5p regulation and function.
- Analysis of nitric oxide production, reactive oxygen species levels, and adhesion molecule expression (ICAM-1, VCAM-1) in HUVECs.
Main Results:
- miR-199a-5p expression was significantly elevated in plasma exosomes and placental tissue of sPE patients.
- Hydrogen peroxide (H2O2) upregulated miR-199a-5p in BeWo cells and exosomes.
- Exosomal miR-199a-5p inhibited SIRT1 expression in HUVECs, leading to decreased nitric oxide, increased reactive oxygen species, and enhanced ICAM-1/VCAM-1 expression.
Conclusions:
- Elevated plasma exosomal miR-199a-5p in sPE may originate from placental oxidative stress.
- Exosomal miR-199a-5p contributes to sPE development by impairing endothelial cell function through SIRT1 inhibition.
Abstract:
Preeclampsia (PE) is a pregnancy complication with high maternal and fetal morbidity and mortality rates. During pregnancy, the concentration of exosomes in the maternal blood circulation would increase, establishing that plasma exosomes play a role in the development of pregnancy. Our previous study implied the important role of exosomal miR-199a-5p in preeclampsia with severe features (sPE). This study aims to reveal the role of exosomal miR-199a-5p in contribution to the development of sPE. The results showed that the expression of miR-199a-5p was significantly higher in plasma exosomes and placenta tissue from patients with sPE than that in normal pregnant women. Additionally, hydrogen peroxide (H2O2) could upregulate the expression of miR-199a-5p in BeWo cells and cell-derived exosomes. In terms of the regulatory effect, exosomal miR-199a-5p was observed to inhibit the expression of SIRT1 in human umbilical venous endothelial cells (HUVECs). Moreover, the treatment of both miR-199a-5p-overexpressed exosomes and SIRT1 inhibitor EX527 could decrease the nitric oxide production, elevate the intracellular reactive oxygen species level, and enhance the expressions of ICAM-1 and VCAM-1 of HUVECs. Thus, our findings suggest that the upregulated plasma exosomal miR-199a-5p in sPE might result from the trophoblast of the impaired placenta under oxidative stress. Furthermore, exosomal miR-199a-5p could impair the endothelial cell function via targeting SIRT1, contributing to the development of preeclampsia.
