ELABELA/APELA Levels Are Not Decreased in the Maternal Circulation or Placenta among Women with Preeclampsia.
The American journal of pathology
American Society for Investigative Pathology
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Pritchard, N., Kaitu'u-Lino, T. J., Gong, S., Dopierala, J., Smith, G., Charnock-Jones, S., & Tong, S. (2018). ELABELA/APELA Levels Are Not Decreased in the Maternal Circulation or Placenta among Women with Preeclampsia.. The American journal of pathology, 188 (8), 1749-1753. https://doi.org/10.1016/j.ajpath.2018.04.008
The genetic deletion of Elabela (encoding the peptide hormone Apelin Receptor Early Endogenous Ligand) produces a preeclampsia-like phenotype in mice. However, evidence linking ELABELA with human disease is lacking. Therefore, we measured placental mRNA and circulating ELABELA in human samples. ELABELA mRNA (measured by RNA-Seq) was unchanged in 82 preeclamptic placentas compared to 82 matched controls (mean difference 0.53 %; 95% CI, -25.9 to 27.0, P=0.78). We measured circulating ELABELA in 32 women with preterm preeclampsia (delivered <34 weeks’ gestation) and 32 matched controls sampled at the same gestational age. There was no difference in circulating ELABELA concentration (median (95% CI) in the preeclamptic cohort 28.5 pg/ml (5.3-63-2) vs 20.5 pg/ml (9.2-58.0) controls; median difference (95% CI) was 8.0 pg/ml (CI -17.7 to 12.1), P=0.43). In contrast, soluble FLT1 (sFLT1, a protein with an established association with preeclampsia) mRNA was elevated in placental tissue (mean difference 34.9%; 95% CI, 16.6 to 53.1, P=0.001), and circulating concentrations were 16.8-fold higher among the preeclamptic cohort (P<0.0001). In conclusion, we were able to recapitulate the well-recognized association between circulating sFLT1 and preeclampsia but there was no such association with ELABELA. Hence, we do not believe that the speculated clinical relevance of observations in the murine model linking ELABELA to preeclampsia are likely to be correct.
Placenta, Humans, Pre-Eclampsia, Peptide Hormones, Case-Control Studies, Prospective Studies, Pregnancy, Adult, Female, Biomarkers
Some of the work described was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme), and project grants from the Medical Research Council (United Kingdom; G1100221) and the Stillbirth and neonatal death society (Sands). The study was also supported by GE Healthcare (donation of 2 Voluson i ultrasound systems for this study) and by the NIHR Cambridge Clinical Research Facility, where research visits took place.
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG52380)
External DOI: https://doi.org/10.1016/j.ajpath.2018.04.008
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278802
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
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