A two-stage model was proposed in which deficient uterine spiral artery remodelling leads to placental ischaemia (stage 1) and the consequent release of antiangiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt-1) or soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and soluble endoglin (sEng), leads to generalized endothelial dysfunction (stage 2). Here, FLT1 is linked to endothelial dysfunction.