Preventing Preeclampsia via the targeted Inhibition of Procoagulant Platelets

Abstract Preeclampsia (PE) is a placenta-mediated thrombotic-inflammatory syndrome. Procoagulant platelets are the main source of platelet microparticles (PMPs), which can result in both pro-inflammatory and pro-thrombotic effects. Therefore, we hypothesized that targeted inhibition of procoagulant platelets would prevent PE via the reduction of PMPs generation. The procoagulant platelet levels in 49 healthy pregnant women and 39 pregnant women with PE were measured and compared. High-performance liquid chromatography coupled with mass spectrometry (LC–MS/MS) was used to investigate the differential proteomes of the platelet proteins isolated from 6 healthy pregnant women and 6 pregnant women with PE. Recombinant protein CD39-Diannexin was constructed for the targeted inhibition of procoagulant platelets. A PE mouse model was developed to investigate whether targeted inhibition of procoagulant platelets could prevent PE. PE patients showed elevated levels of procoagulant platelets and platelet microparticle generation; their platelet proteomics revealed that the proteins involved in complement, coagulation, and inflammation responses were downregulated. Recombinant protein CD39-Diannexin can target the inhibition of procoagulant platelet function both ex vivo and in vivo. This can prevent the PE-like phenotype, characterized by decreased blood pressure, protein/creatine (P/C) ratio, soluble fms-like tyrosine kinase (sFlt-1), decreased pregnancy failure, and reduced placenta inflammasome activation. To conclude, procoagulant platelets are involved in the mechanism underlying PE and the recombinant protein CD39-Diannexin may help prevent PE via the targeted inhibition of procoagulant platelets.