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Preeclampsia: Our Understanding Accelerates

Assessment of maternal anti- and proangiogenic proteins leads to new insights about preeclampsia.

Preeclampsia, a syndrome characterized by hypertension and proteinuria, complicates almost 5% of pregnancies and represents an important cause of maternal and perinatal morbidity and mortality. Soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein that sequesters placental growth factor (PlGF, a proangiogenic protein), plays a role in the pathogenesis of preeclampsia (see also Journal Watch Women’s Health Mar 23 2004). Data from a study in rodents suggest that another antiangiogenic protein, soluble endoglin (sEng), acts with sFlt1 to cause a preeclampsia-like syndrome. Accordingly, these investigators performed a case-control study using blood specimens from nulliparous women who participated in the Calcium for Preeclampsia Prevention trial.

In women who developed preeclampsia compared with normotensive controls, circulating sEng levels were increased at the time of diagnosis as well as during the months prior to the onset of disease. Two to three months before the diagnosis of preeclampsia, increases in sEng were more dramatic among women who developed disease preterm than among those who developed preeclampsia at term. Increased sEng levels were often accompanied by an increased ratio of sFlt1: PlGF. The risk for preeclampsia was highest among women in the highest quartile for both sEng and sFlt1: PlGF. Women with high levels of a single biomarker had lesser elevations in risk.

Comment: Preeclampsia appears to result from the release of circulating factors from the placenta that cause endothelial dysfunction. More specifically, elevations in sEng and the sFlt1: PlGF ratio may play a role in causing this potentially lethal complication of pregnancy. These changes were observed months before the onset of clinical disease; thus, their detection might define new monitoring strategies that could ultimately improve maternal and perinatal outcomes. Even more exciting, advances in our knowledge regarding anti- and proangiogenic proteins may someday lead to the development of proteins tailored for the treatment of preeclampsia.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health September 7, 2006

Citation(s):

Levine RJ et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 2006 Sep 7; 355:992-1005.

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