Fig. 2.

The placental or trophoblast ischemia and hypoxia hypothesis that explains the pathogenesis of PE.

The placenta of PE patients exhibits ischemia and hypoxia, which reduces the expression of PAPP-A and PP-13, and increases the expression of AT1-AA, HIF-1α, and miR-210. The abnormal expression of these proteins induces endothelial damage, inadequate trophoblastic cell invasion, and abnormal placental implantation, further exacerbating placental ischemia and hypoxia. As a negative feedback regulation, trophoblast cells secrete more HGF to promote trophoblast migration and infiltration. The dashed lines in the figure indicate that these biomarkers still need to be verified by more large-scale clinical longitudinal studies as indicators to predict the risk of PE.