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Plasma Exosomal miR-199a-5p Derived from Preeclampsia with Severe Features Impairs Endothelial Cell Function via Targeting SIRT1

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A Correction to this article was published on 12 December 2023

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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.

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Funding

This work was supported by Natural Science Foundation of Sichuan Province (No.2022NSFSC1373), the Luzhou Key R&D Technology Project for Social Development (No. 2021-syf-27), the Doctoral Research Initiation Fund of Affiliated Hospital of Southwest Medical University, and the National Natural Science Foundation of China (No. 81703242).

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Authors and Affiliations

  1. Department of Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China

    Zhirui Chen & Qingqing Luo

  2. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China

    Zhirui Chen, Mengying Wu, Haixia Huang, Hui Tao & Li Zou

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All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. Li Zou and Qingqing Luo contributed to the study design. Zhirui Chen performed experiments and analyzed data. Zhirui Chen, Qingqing Luo, Mengying Wu, Haixia Huang, and Hui Tao contributed to the drafting and revision of the manuscript. Qingqing Luo contributed to funding acquisition.

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Correspondence to Li Zou or Qingqing Luo.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (HUST) (No. 2018S419).

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Chen, Z., Wu, M., Huang, H. et al. Plasma Exosomal miR-199a-5p Derived from Preeclampsia with Severe Features Impairs Endothelial Cell Function via Targeting SIRT1. Reprod. Sci. 29, 3413–3424 (2022). https://doi.org/10.1007/s43032-022-00977-0

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