Two decades of advances in preeclampsia research: molecular mechanisms and translational studies

Abstract

Preeclampsia, a hypertensive disorder of pregnancy, poses a serious threat to the health of women and infants, causing over 75,000 maternal deaths and more than 500,000 infant deaths annually worldwide. Its grim toll is compounded by adverse maternal complications, such as seizures (eclampsia), liver dysfunction, or pulmonary edema. Although interventions like antihypertensives and magnesium sulfate offer partial mitigation of risks to the mother, the definitive remedy remains delivery of the infant and placenta. However, this solution begets iatrogenic prematurity, ushering infants into a neonatal period fraught with serious complications, such as bronchopulmonary dysplasia and necrotizing enterocolitis, as well as other long-term consequences. In 1914, James Young proposed that interference with uterine blood supply to the placenta would lead to placental infarctions that, in turn, would release toxins into the maternal circulation, thus causing eclampsia (summarized in ref. 1). Decades later, during the mid-1980s, Roberts and Taylor hypothesized that preeclampsia is a endothelial disease based on the observation that the endothelium was the predominant cell type injured during preeclampsia and because endothelial injury antedated the clinical manifestations of disease (2). In a 2003 JCI paper, our group reported evidence and posited that elevated levels of soluble fms-like tyrosine kinase 1 (sFLT1) secreted from the placenta acted as the putative “endothelial toxin” that drives the clinical syndrome of preeclampsia (3). Below, we […]