Significance of angiogenic factors imbalance in preeclampsia

Abstract

The role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt-
1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstrated
in multiple clinical and experimental studies. These studies are complemented by animal studies, in
which overexpression of these antiangiogenic factors leads to clinical manifestations similar to PE. Although,
the origin of this disease remains unknown, genetic, environmental, and immunological factors
appear to affect the normal placental development, resulting ultimately in PE. sFlt-1 and sEng inhibit
the proangiogenic properties of the vascular endothelial growth factor (VEGF) and the placental growth
factor (PlGF), affecting the normal vascular development in the placenta and the physiological vascular
adaptations that occur in pregnancy. Exaggerated amounts of sFlt-1 and sEng, produced in the dysfunctional
placenta, are released into the maternal circulation and elevated circulating concentrations
of these antiangiogenic factors are found several weeks prior to the clinical manifestations of the disease.
Multiple studies have reported the capacity of circulating antiangiogenic factor concentrations
to predict PE in asymptomatic low and high risk pregnancies. The reported predictive values of sFlt-1
and sEng are inconsistent across these studies and therefore their clinical use in this population is not
recommended. On the other hand, maternal plasma concentrations of these factors appear to have
a better performance in women with symptoms of PE. Among the possible combinations, the ratios
of sFlt-1/PlGF, PlGF/sFlt-1, and PlGF/Engs seem to have the highest sensitivities and specificities to diagnose
PE as well as the highest predictive values for PE-related adverse outcomes. These properties
support their clinical use in this setting and it is likely those ancillary tests will be incorporated to the
clinical practice in the near future. The participation of antiangiogenic factors in the pathogenesis of
PE, also have stimulated investigation of new targeted therapies. The biological and pharmacokinetic
properties of statins have converted them in one of the most promising preventive therapies for
this disease. Others are investigating agents that directly inhibit the circulating antiangiogenic factors.
In-vitro and pilot clinical studies are currently evaluating the effectiveness, maternal-fetal safety, and
placental transference of these therapies.
Keywords: Angiogenic factors, preeclampsia, placenta growth factor, endothelial vascular growth factor,
endoglin, soluble fms-like tyrosine kinase-