Circulating Angiogenic Factors in the Pathogenesis and Prediction of Preeclampsia

Abstract

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.

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

“…[73][74][75][76][77][78][79][80] Both plasma and amniotic fluid concentrations of sFlt-1 are increased in preeclamptic patients, as well as placental sFlt-1 mRNA. [73][74][75][76][77][78][79][80] Recently, studies have reported that increased sFlt-1 may have a predictive value in diagnosing preeclampsia as concentrations seem to increase before manifestation of overt symptoms (eg, hypertension, proteinuria).…”

“…[73][74][75][76][77][78][79][80] Both plasma and amniotic fluid concentrations of sFlt-1 are increased in preeclamptic patients, as well as placental sFlt-1 mRNA. [73][74][75][76][77][78][79][80] Recently, studies have reported that increased sFlt-1 may have a predictive value in diagnosing preeclampsia as concentrations seem to increase before manifestation of overt symptoms (eg, hypertension, proteinuria). 73,[81][82][83][84] In an elegantly designed study reported several years ago, Maynard et al 85 reported that exogenous administration of sFlt-1 into pregnant rats via adenovirus mediated gene transfer resulted in increased arterial pressure and proteinuria, and decreased plasma free VEGF and PlGF concentrations similar to that observed in the preeclamptic patients.…”

Exploring the Underlying Hormonal Mechanisms of Prenatal Risk Factors for Breast Cancer: A Review and Commentary

“…The etiology of preeclampsia is likely to involve immunologic, inflammatory, and angiogenic abnormalities, and there is a large literature on biological and molecular markers of these processes aimed at early disease prediction and treatment (136)(137)(138)(139). Especially promising are results of research focused on the balance of major angiogenic and antiangiogenic proteins (140).…”

A Study of HELLP Syndrome among Cases of Pre-Eclampsia and Eclampsia: Incidence and Correlation of Laboratory Parameters

“…Many genes have been implicated in the etiology of HELLP syndrome, such as the STOX1 gene, Syncytin Envelope Gene, Mannose Binding Lectin (MBL) gene polymorphism, Factor V leiden mutation, MTHFR deficiency [12]. Vascular endothelial growth factor (VEGF) and mutations of Angiotensin converting enzyme (ACE) have also been implicated in the pathogenesis [20].…”