Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing the release of microparticles

Han Guo, Yuncong Zhang, Yaxin Chu, Shuo Yang, Jie Zhang, Rui Qiao

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Front. Med. ›› 2022, Vol. 16 ›› Issue (6) : 919-931. DOI: 10.1007/s11684-021-0918-6
RESEARCH ARTICLE

Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing the release of microparticles

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Abstract

Preeclampsia (PE) is characterized by placenta-mediated pregnancy complication. The only effective treatment for PE is the delivery of the placenta. However, this treatment may cause preterm birth and neonatal death. Therefore, preventing PE is needed. The mechanism of PE involves abnormal placentation, which leads to the release of anti-angiogenic and inflammatory mediators into maternal circulation. These mediators contribute to systemic vascular dysfunction, inflammatory responses, and excessive thrombin generation. Microparticles (MPs) are reportedly involved in PE by promoting the thromboinflammatory response. This study describes a strategy to prevent PE by reducing MP release using the recombinant protein, diannexin. Results showed that the patients with PE had elevated MP number and procoagulant activity and increased NLRP3 inflammasome activation. Additionally, diannexin remarkably reduced the release of MPs from activated cells by binding to phosphatidylserine exposed on the surface of activated cells. Moreover, in vivo results showed that diannexin could prevent PE-like symptoms by decreasing MPs and NLRP3 inflammasome activation in pregnant mice. Furthermore, diannexin effectively inhibited trophoblast cell activation and NLRP3 inflammasome activation in vitro. These findings suggested that diannexin inhibited MP release and might be an effective therapeutic strategy for preventing PE.

Keywords

preeclampsia / recombinant protein diannexin / microparticle / NLRP3 inflammasome / phosphatidylserin

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Han Guo, Yuncong Zhang, Yaxin Chu, Shuo Yang, Jie Zhang, Rui Qiao. Recombinant protein diannexin prevents preeclampsia-like symptoms in a pregnant mouse model via reducing the release of microparticles. Front. Med., 2022, 16(6): 919‒931 https://doi.org/10.1007/s11684-021-0918-6

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Acknowledgements

The study was supported by Natural Science Foundation of Beijing Municipality (No. 7192222) and National Natural Science Foundation of China (No. 82072352).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-021-0918-6 and is accessible for authorized users.

Compliance with ethics guidelines

Han Guo, Yuncong Zhang, Yaxin Chu, Shuo Yang, Jie Zhang, and Rui Qiao declare that they have no conflicts of interest. For the human studies, all procedures followed were in accordance with the Hospital Research and Ethical Committee (Approval number: IRB00006761-2016055) and the Helsinki Declaration of 1975 revised in 2000. Informed consent was obtained from all patients included in the study. For the animal studies, all institutional and national guidelines for the care and use of laboratory animals were followed.

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