Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Department of Obstetrics and Gynaecology, University of Cambridge; National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre, Cambridge, United Kingdom.
Am J Pathol. 2018 Aug;188(8):1749-1753. doi: 10.1016/j.ajpath.2018.04.008. Epub 2018 May 24.
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.
Apelin 受体早期内源性配体（Elabela；官方名称 APELA）的基因缺失会导致小鼠出现子痫前期样表型。然而，目前缺乏 ELABELA 与人类疾病相关的证据。因此，我们测量了人类样本中的胎盘 mRNA 和循环 ELABELA。与 82 例匹配的对照组相比，82 例子痫前期胎盘的 ELABELA mRNA（通过 RNA 测序测量）没有变化（平均差异 0.53%；95%CI，-25.9 至 27.0；P=0.78）。我们测量了 32 例早产子痫前期（<34 孕周分娩）妇女和 32 例同期匹配对照者的循环 ELABELA。与对照组相比，子痫前期组的循环 ELABELA 浓度没有差异（中位数 28.5 pg/mL；95%CI，5.3 至 63.2 与中位数 20.5 pg/mL；95%CI，9.2 至 58.0 相比）；中位数差异为 8.0 pg/mL（95%CI，-17.7 至 12.1；P=0.43）。相比之下，胎盘组织中可溶性 FLT1（一种与子痫前期有明确关联的蛋白质）mRNA 增加（平均差异 34.9%；95%CI，16.6 至 53.1；P=0.001），子痫前期组的循环浓度高 16.8 倍（P<0.0001）。总之，我们能够重现循环可溶性 FLT1 与子痫前期之间的关联，但与 ELABELA 无关。在小鼠模型中观察到的 ELABELA 与子痫前期之间的关联，推测其临床意义可能不正确。
