Assessing the circulating placental-specific anti-angiogenic protein sFLT-1 e15a in preeclampsia

Preeclampsia is a common obstetric complication globally responsible for a significant burden of maternal and perinatal morbidity and mortality. The anti-angiogenic protein, sFLT-1, plays a central role in its pathophysiology. sFLT-1 is released from a range of tissues into the circulation, where it antagonizes the activity of vascular endothelial growth factor and placental growth factor leading to endothelial dysfunction. The resulting widespread endothelial dysfunction produces the clinical features of preeclampsia including hypertension and proteinuria. Multiple splice variants of sFLT-1 have been identified, with one, known as sFLT-1 e15a, present only in humans and higher-order primates. This sFLT-1 variant is also the main form of sFLT-1 produced by the placenta. Recent work has shown that sFLT-1 e15a is significantly elevated in the placenta and circulation of women with preeclampsia. It is also biologically active, capable of causing endothelial dysfunction and end-organ dysfunction seen in preeclampsia. Indeed, overexpression of sFLT-1 e15a in mice recapitulates the preeclamptic phenotype in pregnancy. No commercial assay currently exists to analyze sFLT-1 e15a protein levels. Here, a new ELISA method to determine circulating sFLT-1 variant levels is described.