Chair of Gynecology and Obstetrics, Jagiellonian University Medical College, Kraków, Poland.
Department of Clinical Pharmacology, Jagiellonian University Medical College, Kraków, Poland.
Folia Med Cracov. 2022 Jun 29;62(1):71-88. doi: 10.24425/fmc.2022.141692.
Preeclampsia (PE) is a condition characterized by high blood pressure and significant proteinuria in pregnant women. It affects about 7% pregnancies and can be cause of fetal and maternal morbidity and mortality. During pregnancy, a physiological overexpression of the Renin-Angiotensin System (RAS) components is observed, including increased plasma Ang II level. Dysregulation of RAS in placenta may contribute to preeclampsia and uterine growth retardation. The aim of the study was to evaluate the Ang I metabolism in human preeclamptic placentas and to compare to normal pregnancies condition.
Fragments of placental tissues were collected right after ceasarian section from PE and physiological pregnancies. Tissues were incubated in Krebs buffer in the presence of Ang I. Evaluation of Ang I metabolites in incubating fluid was performed by LC/MS/MS method. mRNA expression of main RAS components was measured by RT-PCR.
Pattern of angiotensin metabolites did not differ between groups. The main products were Ang 1-7 and Ang II. Comparing to control group, more than 3-fold lower production of Ang II and Ang 1-7 in preeclampsia was observed. mRNA expressions of ACE and AT1 were significantly decreased in pre- eclamptic placentas, whereas higher expression of mRNA of ACE2 and MAS receptor were observed.
Production of Ang 1-7 by PE placentas was significantly lower than in control group. Significantly decreased mRNA expression of ACE and AT1 receptor and lower production of Ang II in placentas of PE patients suggest that placental Ang II/ACE/AT1r pathway could be less important than Ang 1-7/ACE-2/MASr pathway in development of preeclampsia, but this requires further investigations.
子痫前期(PE)是一种以孕妇高血压和大量蛋白尿为特征的疾病。它影响约 7%的妊娠,并可能导致胎儿和母体发病率和死亡率。在怀孕期间,观察到肾素-血管紧张素系统(RAS)成分的生理过度表达,包括血浆 Ang II 水平增加。胎盘 RAS 的失调可能导致子痫前期和子宫生长迟缓。本研究旨在评估人类子痫前期胎盘的 Ang I 代谢,并与正常妊娠情况进行比较。
剖宫产术后立即从 PE 和生理妊娠中收集胎盘组织片段。组织在 Krebs 缓冲液中孵育,存在 Ang I。通过 LC/MS/MS 方法评估孵育液中 Ang I 代谢物。通过 RT-PCR 测量主要 RAS 成分的 mRNA 表达。
各组之间的血管紧张素代谢物模式没有差异。主要产物是 Ang 1-7 和 Ang II。与对照组相比,子痫前期的 Ang II 和 Ang 1-7 产生量低 3 倍以上。PE 胎盘中 ACE 和 AT1 的 mRNA 表达明显降低,而 ACE2 和 MAS 受体的 mRNA 表达升高。
PE 胎盘产生的 Ang 1-7 明显低于对照组。PE 患者胎盘中 ACE 和 AT1 受体的 mRNA 表达明显降低,Ang II 产生减少,提示胎盘 Ang II/ACE/AT1r 途径在子痫前期的发展中可能不如 Ang 1-7/ACE-2/MASr 途径重要,但这需要进一步研究。