The apelinergic-axis in human preeclamptic pregnancies: A systematic review.

The apelinergic-axis (Apelin, Elabela and their receptor APJ) is involved in many physiological and pathological processes. Both Elabela/APJ and Apelin/APJ are implicated in the pathophysiology of preeclampsia in rodents. However, the findings regarding the apelinergic axis in human preeclamptic placental development have been rather conflicting. In this systematic review we present an overview of the current evidence regarding the pathophysiological role of Apelin, Elabela and their receptor in human preeclamptic pregnancies. The databases used for this systematic review were Pubmed, Scopus, Google Scholar and ClinicalTrials.gov. The reference lists of the selected studies were also screened for any additional studies. The last search was performed on the 25th of March 2019. Thirteen studies were included and subjected to quality assessment so that only high quality datasets were finally selected and included in this systematic evaluation. In total, 410 women that developed preeclampsia or IUGR and 409 healthy control pregnancies were included. The findings of this review suggest that circulating Apelin levels are increased in early onset/severe preeclamptic patients while Apelin levels in severe preeclamptic placenta tissues appear to show the opposite. Circulating Elabela levels in early-onset preeclamptic women do not differ from controls, while its levels in late-onset preeclampsia remain inconclusive. The studies on Elabela and APJ expression in placental tissues require larger sample sizes with defined preeclampsia subtypes to draw any definite conclusions. Large cohort studies with affected and control groups matched for Body Mass Index and gestational age at sampling are essential in order to substantiate other current findings.