Preeclampsia Pathogenesis

Abstract

Preeclampsia, a major killer of mother and fetuses, has traditionally been called the disease of theories, but research these past decades is changing all of that. Early observations related to this disorder were that all of the signs and symptoms typically resolve rapidly after the delivery of the placenta. Thus, it was natural to focus on this organ as the source of the disease. In this respect, 2 antiangiogenic proteins, overproduced in the placenta, that gain access to the maternal circulation have become candidate molecules responsible for phenotypic preeclampsia. One is soluble Fms-like tyrosine kinase-1 (sFlt1), an endogenous inhibitor of vascular endothelial growth factor and placental growth factor signaling that may regulate placental angiogenesis, and the other is soluble endoglin, a circulating coreceptor that may inhibit transforming growth factor-β1 signaling in the vasculature.1 Maternal blood levels of both of these antiangiogenic proteins are increased in preeclamptic patients compared with those in uncomplicated pregnancies weeks to months before overt signs and symptoms.1 Adenoviral overexpression of sFlt1 and soluble endoglin in rodents produces preeclampsia-like phenotypes, including severe hypertension, proteinuria, glomerular endotheliosis, and features resembling the HELLP syndrome (hemolysis, elevated liver enzymes, low platelet syndrome) in humans.2 The increased risk of preeclampsia in women with multifetal pregnancies, trisomy 13, primiparity, high altitudes, and mirror syndrome may also be explained by alterations in circulating antiangiogenic factors (reviewed in Reference 3). However, as data supporting a significant role …