Telling swelling. sFlt1 caused swollen glomeruli (right)--a known symptom of human preeclampsia--in pregnant rats’ kidneys.

Protein for High-Pressure Pregnancies

Researchers have shed new light on preeclampsia, the leading cause of death for pregnant women. The study raises hopes for a new treatment.

Preeclampsia, which occurs in at least 5% of all pregnancies, has been called a "disease of theories" because of its elusive nature. It damages a woman's blood vessels, resulting in high blood pressure, swelling, and protein leakage in the urine. The disease can result in serious liver and renal problems, cerebral edema, and life-threatening seizures. Symptoms appear after the 20th week of pregnancy and are usually detected by routine monitoring of women's blood pressure and urine. Currently, the only “therapy” is a premature delivery, which puts the baby at risk of complications.

Fishing for a cause, Harvard nephrologist Ananth Karumanchi and his colleagues carried out a gene-expression study on placenta samples, collected immediately after delivery, from 17 healthy women and 21 others with preeclampsia. They discovered that the placentas of preeclampsia patients showed more activity in the gene for sFlt1, a protein that blocks the effects of vascular endothelial growth factor and placental growth factor, two key proteins necessary for an adequate placental development and normal blood vessel health. In blood samples collected during pregnancy, sFlt1 levels turned out to be almost five times higher in the women affected by preeclampsia.

To find out the role sFlt1 might play, the researchers injected the protein into the tail vein of pregnant rats. It caused hypertension and large amounts of protein in their urine. What's more, microscopic studies of renal tissue from affected rats had the hallmarks of renal biopsies during human preeclampsia, the scientists report in the 4 March Journal of Clinical Investigation.

The study sheds "unprecedented light" on the complex mechanisms behind preeclampsia, says geneticist Aernout Luttun of the Katholieke Universiteit Leuven in Belgium. The study also raises hopes that researchers may find a new preeclampsia treatment by blocking SFlt1, he says.

Related sites
Abstract of the paper
More about preecclampsia, from the Preecclampsia Foundation