Tenafly High School, Tenafly, USA.
Stroke Trials Unit (School of Medicine), University of Nottingham, Nottingham, UK.
Placenta. 2023 Mar 24;134:9-14. doi: 10.1016/j.placenta.2023.02.006. Epub 2023 Feb 22.
Endoplasmic reticulum resident protein 44 (ERp44) is a zinc-metalloprotein, regulating Endoplasmic reticulum aminopeptidase 1 (ERAP1) and Angiotensin II (Ang II). We explored placental ERp44 expression and components of the renin-angiotensin-system (RAS) in pre-eclampsia (PE), correlating these to ERAP1 expression and placental zinc concentrations.
Placental tissue, taken at time of delivery in normotensive women or women with PE (n = 12/group), were analysed for ERp44, AT1R, AT2R and AT4R by qPCR. Protein ERp44 expression was measured by immunohistochemistry and compared to previously measured ERAP1 expression. Placental zinc was measured by inductively-coupled-mass-spectrometry.
ERp44 gene/protein expression were increased in PE (P < 0.05). AT1R expression was increased (P = 0.02) but AT4R decreased (P = 0.01) in PE, compared to normotensive controls. A positive association between ERp44 and AT2R expression was observed in all groups. ERp44 was negatively correlated with ERAP1 protein expression in all samples. Placental zinc concentrations were lower in women with PE (P = 0.001) and negatively associated with ERp44 gene expression.
Increased placental ERp44 could further reduce ERAP1 release in PE, potentially preventing release of Ang IV and thus lowering levels of Ang IV which consequently diminishes the possibility of counterbalancing the activity of vasoconstrictive, Ang II. The lower placental zinc may contribute to dysfunction of the ERp44/ERAP1 complex, exacerbating the hypertension in PE.
内质网驻留蛋白 44（ERp44）是一种锌金属蛋白酶，调节内质网氨肽酶 1（ERAP1）和血管紧张素 II（Ang II）。我们探讨了先兆子痫（PE）中胎盘 ERp44 的表达和肾素-血管紧张素系统（RAS）的组成部分，将这些与 ERAP1 的表达和胎盘锌浓度相关联。
在正常血压妇女或患有 PE 的妇女分娩时采集胎盘组织（每组 n=12），通过 qPCR 分析 ERp44、AT1R、AT2R 和 AT4R 的表达。通过免疫组织化学测量 ERp44 蛋白表达，并与之前测量的 ERAP1 表达进行比较。通过电感耦合质谱法测量胎盘锌浓度。
PE 中 ERp44 基因/蛋白表达增加（P<0.05）。与正常血压对照组相比，PE 中 AT1R 表达增加（P=0.02），而 AT4R 表达减少（P=0.01）。在所有组中均观察到 ERp44 与 AT2R 表达之间存在正相关。在所有样本中，ERp44 与 ERAP1 蛋白表达呈负相关。PE 妇女的胎盘锌浓度较低（P=0.001），与 ERp44 基因表达呈负相关。
胎盘 ERp44 的增加可能进一步减少 PE 中 ERAP1 的释放，从而潜在地阻止 Ang IV 的释放，从而降低 Ang IV 的水平，从而降低拮抗血管收缩性 Ang II 的可能性。较低的胎盘锌可能导致 ERp44/ERAP1 复合物功能障碍，加剧 PE 中的高血压。
