Yong Hannah E J, Murthi Padma, Wong May H, Kalionis Bill, Cartwright Judith E, Brennecke Shaun P, Keogh Rosemary J
Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
Department of Perinatal Medicine Pregnancy Research Centre and The University of Melbourne, Department of Obstetrics and Gynaecology, The Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia.
Pregnancy Hypertens. 2015 Oct;5(4):346-53. doi: 10.1016/j.preghy.2015.09.006. Epub 2015 Sep 26.
Activin A, a TGFβ family member, circulates in the maternal blood at increasing concentrations throughout gestation during a healthy pregnancy. The circulating concentration of activin A is further increased in pre-eclampsia (PE), a hypertensive disorder of pregnancy that is marked by systemic maternal vascular endothelial cell dysfunction. The effect of increasing activin A concentrations on the maternal vascular endothelium is unknown. The study aim was to investigate the effect of physiological and pathological activin A concentrations observed in normotensive and PE pregnancies respectively, on vascular endothelial cell function.
Immunostaining demonstrated the presence of the activin A receptor, ACVR2A, in SGHEC-7 cells used to model the vascular endothelium. SGHEC-7 cells were treated with activin A concentrations representative of concentrations throughout gestation in normotensive (0-10ng/ml) and PE (50ng/ml) pregnancies. xCELLigence functional assays revealed that normotensive activin A concentrations increased SGHEC-7 proliferation and migration, which was inhibited by PE concentrations. Additionally, fluorescence based assays showed that PE concentrations increased endothelial permeability. None of the tested activin A concentrations affected cell apoptosis. PE concentrations also resulted in an imbalance of the vasoactive factors eNOS, PTGIS and EDN1, as determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays.
Compared with normotensive activin A concentrations, the higher PE activin A concentrations resulted in abnormal endothelial functions, which may contribute to the systemic maternal vascular endothelial cell dysfunction observed in the disorder.
激活素A是转化生长因子β（TGFβ）家族成员，在正常妊娠期间，其在母血中的循环浓度在整个孕期不断升高。在子痫前期（PE）中，激活素A的循环浓度会进一步升高，子痫前期是一种妊娠高血压疾病，其特征是母体全身血管内皮细胞功能障碍。激活素A浓度升高对母体血管内皮的影响尚不清楚。本研究旨在分别探讨在血压正常和子痫前期妊娠中观察到的生理和病理激活素A浓度对血管内皮细胞功能的影响。
免疫染色显示，在用于模拟血管内皮的SGHEC-7细胞中存在激活素A受体ACVR2A。用代表血压正常（0-10ng/ml）和子痫前期（50ng/ml）妊娠整个孕期浓度的激活素A处理SGHEC-7细胞。xCELLigence功能分析显示，血压正常时的激活素A浓度可增加SGHEC-7细胞的增殖和迁移，而子痫前期浓度则抑制这种作用。此外，基于荧光的分析表明，子痫前期浓度会增加内皮通透性。所测试的激活素A浓度均未影响细胞凋亡。通过定量实时聚合酶链反应和酶联免疫吸附测定法确定，子痫前期浓度还导致血管活性因子内皮型一氧化氮合酶（eNOS）、前列腺素I合成酶（PTGIS）和内皮素1（EDN1）失衡。
与血压正常时的激活素A浓度相比，子痫前期较高的激活素A浓度导致内皮功能异常，这可能导致该疾病中观察到的母体全身血管内皮细胞功能障碍。
