Amraoui F, Hassani Lahsinoui H, Boussata S, Keijser R, Veenboer G J M, Middeldorp S, van der Post J A M, Ris-Stalpers C, Afink G B, van den Born B J H
Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands; Reproductive Biology Laboratory, Academic Medical Center, Amsterdam, The Netherlands.
Placenta. 2015 Nov;36(11):1218-24. doi: 10.1016/j.placenta.2015.09.008. Epub 2015 Sep 16.
The endothelial glycocalyx, consisting of membrane-bound proteoglycans and attached glycosaminoglycans plays an important role in vascular homeostasis. We aimed to assess whether glycocalyx mRNA transcripts are differentially expressed in placental tissue of pre-eclamptic and normotensive women.
We evaluated the expression of transcripts encoding for proteins involved in glycocalyx synthesis and degradation using a microarray analysis of placental mRNA obtained from pre-eclamptic and normotensive women. Participants were recruited from the department of obstetrics at a university hospital in Amsterdam, The Netherlands. The most prominent differentially expressed transcript was validated by qPCR on 112 additional placenta samples.
Of 78 preselected genes involved in glycocalyx synthesis and degradation, only HS3ST3A1 mRNA was differentially expressed in placental tissue obtained from pre-eclamptic women (N = 12) compared to normotensive women (N = 12, fold change = 0.61, p = 0.02). Validation with qPCR in additional placental samples of 64 normotensive and 48 pre-eclamptic women confirmed that normalized mRNA expression of HS3ST3A1 was decreased by 27% (95% CI 14%-41%) in placental tissue obtained from pre-eclamptic compared to normotensive women (p < 0.001). HS3ST3A1 expression was positively correlated with neonatal birth weight in normotensive women (r = 0.35, p < 0.01) and inversely correlated with mean arterial pressure of women with pre-eclampsia (r = 0.32, p = 0.02).
The mRNA expression of HS3ST3A1, which encodes for a 3-O sulfating enzyme of heparan sulfate (3-OST-3A1), is decreased in pre-eclamptic placental tissue. Expression of this glycocalyx synthesis transcript is correlated with maternal blood pressure and neonatal birth weight, suggesting a possible role in pre-eclampsia-associated placental dysfunction.
由膜结合蛋白聚糖和附着的糖胺聚糖组成的内皮糖萼在血管稳态中起重要作用。我们旨在评估糖萼mRNA转录本在子痫前期和血压正常女性的胎盘组织中是否存在差异表达。
我们使用从子痫前期和血压正常女性获得的胎盘mRNA进行微阵列分析，评估参与糖萼合成和降解的蛋白质编码转录本的表达。参与者来自荷兰阿姆斯特丹一家大学医院的妇产科。通过对另外112个胎盘样本进行qPCR验证了最显著差异表达的转录本。
在78个预先选择的参与糖萼合成和降解的基因中，与血压正常女性（N = 12）相比，子痫前期女性（N = 12）获得的胎盘组织中只有HS3ST3A1 mRNA存在差异表达（倍数变化 = 0.61，p = 0.02）。对另外64名血压正常和48名子痫前期女性的胎盘样本进行qPCR验证，结果证实，与血压正常女性相比，子痫前期女性获得的胎盘组织中HS3ST3A1的标准化mRNA表达降低了27%（95% CI 14%-41%）（p < 0.001）。在血压正常女性中，HS3ST3A1表达与新生儿出生体重呈正相关（r = 0.35，p < 0.01），而与子痫前期女性的平均动脉压呈负相关（r = 0.32，p = 0.02）。
编码硫酸乙酰肝素3-O硫酸化酶（3-OST-3A1）的HS3ST3A1的mRNA表达在子痫前期胎盘组织中降低。这种糖萼合成转录本的表达与母体血压和新生儿出生体重相关，提示其在子痫前期相关胎盘功能障碍中可能发挥作用。
