Friday, August 1, 2008

sFlt-1 & Pre-eclampsia

One of the most exciting new advances in the field of pre-eclampsia has been the relatively recent discovery of the role of sFlt-1 in pre-eclampsia.

sFlt-1 (which stands for "soluble Fms-like tyrosine kinase) is a circulating protein which is able to bind to and inhibit vascular endothelial growth factor (VEGF). It was initially noted that there is an increased level of sFlt-1 in the blood of pregnant women with pre-eclampsia which rapidly goes away following delivery. Furthermore, injection of sFlt-1 into pregnant rats results in hypertension, proteinuria, and endothelial dysfunction causing a thrombotic microangiopathy pattern of injury (all the cardinal features of pre-eclampsia), implying that the elevated sFlt-1 levels are not just associative with pre-eclampsia but also causative (see Maynard et al, JCI 2003). The current model is that VEGF is required for maintenance of a healthy endothelium; the release of sFlt-1 by placental cells inhibits VEGF activity and thereby deprives endothelial cells of this necessary stimulus.

One might therefore be able to treat pre-eclampsia by designing inhibitors of sFlt-1, or perhaps by overwhelming the inhibitor with exogenous VEGF.

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