Obstetrics and Gynaecology - Research Publications

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Author: Pritchard, Natasha × Author: Tong, Stephen × End date: 2019 × Start date: 2018 × Type: Journal Article ×

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    ELABELA/APELA Levels Are Not Decreased in the Maternal Circulation or Placenta among Women with Preeclampsia
    Pritchard, N ; Kaitu'u-Lino, TJ ; Gong, S ; Dopierala, J ; Smith, GCS ; Charnock-Jones, DS ; Tong, S (ELSEVIER SCIENCE INC, 2018-08)
    The genetic deletion of apelin receptor early endogenous ligand (Elabela; official name APELA) 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 sequencing) was unchanged in 82 preeclamptic placentas compared with 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 at <34 weeks' gestation) and 32 matched controls sampled at the same gestational age. There was no difference in circulating ELABELA concentrations in the preeclamptic cohort compared with controls (median, 28.5 pg/mL; 95% CI, 5.3 to 63.2 versus median, 20.5 pg/mL; 95% CI, 9.2 to 58.0, respectively); the median difference was 8.0 pg/mL (95% CI, -17.7 to 12.1; P = 0.43). In contrast, soluble FLT1 (a protein with an established association with preeclampsia) mRNA was increased 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 association between circulating soluble FLT1 and preeclampsia, but there was no association with ELABELA. The speculated clinical relevance of observations in the murine model linking ELABELA to preeclampsia likely are incorrect.
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    Circulating GATA2 mRNA is decreased among women destined to develop preeclampsia and may be of endothelial origin
    Whigham, C-A ; MacDonald, TM ; Walker, SP ; Pritchard, N ; Hannan, NJ ; Cannon, P ; Tuong, VN ; Hastie, R ; Tong, S ; Kaitu'u-Lino, TJ (NATURE PORTFOLIO, 2019-01-18)
    Preeclampsia is a pregnancy complication associated with elevated placental secretion of anti-angiogenic factors, maternal endothelial dysfunction and organ injury. GATA2 is a transcription factor expressed in the endothelium which regulates vascular homeostasis by controlling transcription of genes and microRNAs, including endothelial miR126. We assessed GATA2 and miR126 in preeclampsia. Whole blood circulating GATA2 mRNA and miR126 expression were significantly decreased in women with established early-onset preeclampsia compared to gestation-matched controls (p = 0.002, p < 0.0001, respectively). Using case-control groups selected from a large prospective cohort, whole blood circulating GATA2 mRNA at both 28 and 36 weeks' gestation was significantly reduced prior to the clinical diagnosis of preeclampsia (p = 0.012, p = 0.015 respectively). There were no differences in GATA2 mRNA or protein expression in preeclamptic placentas compared to controls, suggesting the placenta is an unlikely source. Inducing endothelial dysfunction in vitro by administering either tumour necrosis factor-α or placenta-conditioned media to endothelial cells, significantly reduced GATA2 mRNA expression (p < 0.0001), suggesting the reduced levels of circulating GATA2 mRNA may be of endothelial origin. Circulating GATA2 mRNA is decreased in women with established preeclampsia and decreased up to 12 weeks preceding onset of disease. Circulating mRNAs of endothelial origin may be a novel source of biomarker discovery for preeclampsia.