The elusive preeclampsia factor discovered?

Eclampsia, the occurrence of often fatal seizures during pregnancy, is preceded by a condition called preeclampsia. Preeclampsia itself is a serious complication of pregnancy and affects up to 5% of pregnant women. Diagnosed in its early stages by elevated blood pressure and protein levels in the urine, it is the major cause of premature birth and perinatal child death and accounts for approximately 15% of all maternal deaths. Despite decades of intensive research, we still do not know what causes preeclampsia.

In preeclamptic women, blood flow to the placenta is reduced, and the supply of oxygen is decreased. Low placental oxygen levels have been proposed to trigger the release of unknown factors in the placenta that mediate a rapid and unpredictable progression to numerous multisystem complications involving the maternal liver, kidneys, lungs, blood and nervous systems. Two articles in the March 3 issue of the Journal of Clinical Investigation now shed new light on the pathophysiology of this disease. In the first article, S. Ananth Karumanchi and colleagues at Beth Israel Deaconess Medical Center in Boston report that preeclampsia is associated with elevated levels of a protein called sFlt1. To test whether sFlt1 is responsible for the problems in women with preeclampsia, the scientists treated pregnant and non-pregnant rats with this protein. Irrespective of pregnancy, the exposed rats exhibited several of the hallmark clinical and pathological features of preeclampsia, providing a strong argument for a causal role for sFlt1.

sFlt1 binds to and "mops up" a group of proteins--called angiogenic factors--which promote the growth of new blood vessels and are involved in maintenance of the adult vasculature. Elevated levels of sFlt1 presumably reduce the circulating levels of angiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor, below a threshold nece

Contact: Brooke Grindlinger
Journal of Clinical Investigation

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