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

作     者：Han Guo Yuncong Zhang Yaxin Chu Shuo Yang Jie Zhang Rui Qiao Han Guo;Yuncong Zhang;Yaxin Chu;Shuo Yang;Jie Zhang;Rui Qiao

作者机构：Laboratory MedicinePeking University Third HospitalBeijing100191China Department of Clinical LaboratoryPeking University International HospitalBeijing102206China 

出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)

年 卷 期：2022年第16卷第6期

页      面：919-931页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100211[医学-妇产科学] 10[医学] 

基　　金：supported by Natural Science Foundation of Beijing Municipality(No.7192222) National Natural Science Foundation of China(No.82072352). 

主　　题：preeclampsia recombinant protein diannexin microparticle NLRP3 inflammasome phosphatidylserin 

摘      要：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.