Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia.
Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia.
Pregnancy Hypertens. 2019 Apr;16:16-25. doi: 10.1016/j.preghy.2019.02.003. Epub 2019 Feb 10.
Preeclampsia is a pregnancy complication associated with elevated placental secretion of anti-angiogenic factors, maternal endothelial dysfunction and end-organ injury. Adrenomedullin (ADM) is a pro-angiogenic peptide hormone which regulates blood pressure and vascular integrity. It is highly expressed in both the placenta and vascular endothelial cells. We performed a nested case-control study, selected from a large prospective cohort of over 2000 participants. Circulating ADM mRNA was reduced at both 28 (n = 39 vs 248 controls, p = 0.005) and 36 weeks' of pregnancy (n = 39 vs 205 controls, p < 0.0001) in those destined to develop term preeclampsia. It was also significantly reduced in the circulation of women with established early-onset preeclampsia (n = 34 vs 21 controls, p = 0.01). ADM mRNA (n = 34 vs 12 controls) and protein (n = 53 vs 17 controls) were significantly decreased in placental tissue from women with early-onset preeclampsia (p = 0.02, p = 0.0002 respectively), suggesting the placenta is a possible source of the reduced circulating mRNA. Functional studies in primary endothelial cells revealed significantly reduced ADM mRNA expression when cells were exposed to cytotrophoblast conditioned media (derived from normotensive pregnancies, p < 0.0001) or TNFα (p < 0.0001), suggesting another possible source of reduced circulating ADM mRNA is the endothelium. Circulating ADM mRNA, but not protein, is reduced 10-12 weeks before the diagnosis of term preeclampsia. It may be of endothelial or placental origin. Whole blood mRNA is a rich source of potential biomarker discovery in the prediction of preeclampsia.
子痫前期是一种与胎盘分泌抗血管生成因子、母体血管内皮功能障碍和靶器官损伤有关的妊娠并发症。肾上腺髓质素（ADM）是一种促血管生成肽激素，可调节血压和血管完整性。它在胎盘和血管内皮细胞中均高度表达。我们进行了一项巢式病例对照研究，从一个超过 2000 名参与者的大型前瞻性队列中选择。在那些注定要发展为足月子痫前期的患者中，28 周（n=39 与 248 名对照，p=0.005）和 36 周（n=39 与 205 名对照，p<0.0001）时，循环 ADM mRNA 减少。在已经确诊的早发型子痫前期患者（n=34 与 21 名对照，p=0.01）中，循环 ADM mRNA 也显著减少。早发型子痫前期患者胎盘组织中的 ADM mRNA（n=34 与 12 名对照，p=0.02）和蛋白（n=53 与 17 名对照，p=0.0002）也显著减少，这表明胎盘可能是循环 mRNA 减少的来源。原代内皮细胞的功能研究显示，当细胞暴露于正常妊娠来源的滋养细胞条件培养基（p<0.0001）或 TNFα（p<0.0001）时，ADM mRNA 表达显著降低，这表明内皮细胞是循环 ADM mRNA 减少的另一个可能来源。循环 ADM mRNA，而不是蛋白，在足月子痫前期诊断前 10-12 周减少。它可能来自内皮细胞或胎盘。全血 mRNA 是子痫前期预测中潜在生物标志物发现的丰富来源。
