Protein Biomarkers Portend Onset of Preeclampsia

Abnormally high circulating levels of two proteins produced by the placenta may be responsible for the development of preeclampsia, according to a new study.

Researchers from Beth Israel Deaconess Medical Center (Boston, MA, USA) conducted a study of healthy women who have never given birth to a child in a trial called CPEP (Calcium for PreEclampsia Prevention). They found that endoglin--highly expressed on cell membranes of vascular endothelium--is up-regulated in preeclampsia, releasing soluble endoglin, an antiangiogenic protein, into the maternal circulation. Levels of the other antiangiogenic protein, soluble fms-like tyrosine kinase 1 (sFlt1), which sequesters proangiogenic placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), also rose, beginning two to three months before the onset of clinical disease. The study was reported in the September 7, 2006, issue of the New England Journal of Medicine.

These findings, along with rodent studies, suggest that these two protein biomarkers, each of which causes endothelial dysfunction by a different mechanism, may contribute to preeclampsia. Prospective longitudinal studies are needed to assess whether these biomarkers can predict the imminent onset of clinical disease, the researchers added.

"Possible treatments might involve reducing levels of these two antiangiogenic factors or adding more of the molecules they remove from the bloodstream,” said lead author Richard Levine, M.D. However, he cautioned that attempts to develop a drug treatment would need to proceed cautiously, since restoring normal blood pressure and blood flow to the mother's circulatory system might deprive the fetus of blood.

The prevailing theory, according to the researchers, is that when the placenta cannot absorb sufficient oxygen from the mother's blood, it secretes these two biomarkers into the mother's blood stream. In response, the mother's blood pressure rises, forcing more blood into the placenta.



Related Links:
Beth Israel Deaconess Medical Center