Published Online
on October 17, 2005

A more recent version of this article appeared on November 1, 2005

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Submitted on July 12, 2005
Revised on July 19, 2005

Circulating Angiogenic Factors in the Pathogenesis and Prediction of Preeclampsia

Chun Lam; Kee-Hak Lim; and S. Ananth Karumanchi^*

From the Renal Division (C.L., S.A.K.), Department of Medicine, and the Department of Obstetrics and Gynecology (K.-H.L., S.A.K.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: sananth{at}bidmc.harvard.edu.

Abstract--Preeclampsia is a major cause of maternal, fetal, and neonatal mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, high blood pressure and proteinuria, are due in part to excess circulating soluble fms-like tyrosine kinase-1 concentrations. Soluble fms-like tyrosine kinase-1 is an endogenous antiangiogenic protein that is made by the placenta and acts by neutralizing the proangiogenic proteins vascular endothelial growth factor and placental growth factor. High serum soluble fms-like tyrosine kinase-1 and low serum free placental growth factor and free vascular endothelial growth factor have been observed in preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia but also antedate clinical symptoms by several weeks. Therefore, this raises the possibility of measuring circulating angiogenic proteins in the blood and the urine as a diagnostic and screening tool for preeclampsia. The availability of a test to predict preeclampsia would be a powerful tool in preventing preeclampsia-induced mortality, especially in developing nations, where high-risk specialists are limited. This review will summarize our current understanding of the role of circulating angiogenic proteins in the pathogenesis and clinical diagnosis/prediction of preeclampsia.

Key words: angiogenesis • vasculature • proteinuria • hypertension, pregnancy • preeclampsia

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