Are the Cognitive Alterations Present in Children Born From Preeclamptic Pregnancies the Result of Impaired Angiogenesis? Focus on the Potential Role of the VEGF Family.

Evelyn Lara,José Leon,Pablo Torres-Vergara,Jesenia Acurio,Jeffrey Penny,Carlos Escudero

doi:10.3389/fphys.2018.01591

Abstract

Evidence from clinical studies has proposed that children born from preeclamptic women have a higher risk of suffering neurological, psychological, or behavioral alterations. However, to date, the mechanisms behind these outcomes are poorly understood. Here, we speculate that the neurodevelopmental alterations in the children of preeclamptic pregnancies result from impaired angiogenesis. The pro-angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are key regulators of both vascular and neurological development, and it has been widely demonstrated that umbilical blood of preeclamptic pregnancies contains high levels of soluble VEGF receptor type 1 (sFlt-1), a decoy receptor of VEGF. As a consequence, this anti-angiogenic state could lead to long-lasting neurological outcomes. In this non-systematic review, we propose that alterations in the circulating concentrations of VEGF, PlGF, and sFlt-1 in preeclamptic pregnancies will affect both fetal cerebrovascular function and neurodevelopment, which in turn may cause cognitive alterations in post-natal life.

Highlights

Preeclampsia is a multisystemic syndrome of unknown etiology that affects pregnant women after 20 weeks of gestation
Previous reports have proposed that anti-angiogenic factors, including the soluble fms-1-like tyrosine kinase-1, and soluble endoglin are responsible for the endothelial dysfunction present in preeclampsia
A limited number of studies have investigated the effect of sFlt-1 on brain development, including those of Carver et al (2014) which report that, in a mouse model of preeclampsia, adenoviral transfer of sFlt-1 to the mother was associated with sex-dependent neuroanatomical alterations in the offspring at 6 months of age, which were partly counteracted by treating mothers with pravastatin (Carver et al, 2014)

Summary

Introduction

Preeclampsia is a multisystemic syndrome of unknown etiology that affects pregnant women after 20 weeks of gestation. We extend this concept to propose that impaired angiogenesis affects the cognitive development of children born from preeclamptic women.

Results

Conclusion