Research Unit in Reproductive Medicine, Hospital Gabriel Mancera, Instituto Mexicano del Seguro Social, México DF, Mexico.
J Hypertens. 2010 Apr;28(4):834-41. doi: 10.1097/HJH.0b013e3283376cc6.
Recent studies have demonstrated that stimulating autoantibodies against the angiotensin II type 1 receptor (AT1R-AA) are frequently detected in the sera from women with preeclampsia, suggesting that they may play an important role in the pathogenesis of this disease. Nevertheless, the real clinical significance of AT1R-AA in preeclampsia is still controversial due to the paucity of appropriate large comparative studies that require cumbersome, time-consuming, and expensive bioassays to detect AT1R-AA. At present, the prevalence of AT1R-AA in large populations of preeclamptic women is unknown. In an attempt to clarify this issue, we assessed the presence and potential clinical significance of AT1R-AA in a large population of Mexican-Mestizo women with preeclampsia.
Using a cross-sectional design, we determined the presence of AT1R-AA in 525 pregnant women (99 healthy pregnant, 96 with mild preeclampsia, and 330 with severe preeclampsia) by a new bioassay that employs human embryonic kidney-293 cells stably expressing the recombinant rat AT1R and a 4x nuclear factor of activated T cells responsive luciferase construct as well as by the reference assay in Chinese hamster ovary (CHO) cells.
We found that IgG obtained from sera of healthy pregnant women and patients with preeclampsia were unable to induce luciferase activity in both HEK-293 and Chinese hamster ovary cells expressing functional angiotensin II receptor type 1. Therefore, the frequency of patients with AT1R-AA was zero.
We concluded that in Mexican-Mestizo women agonistic AT1R-AA cannot be invoked as a factor involved in the pathogenesis of preeclampsia. Whether these findings can be attributed to genetic or environmental factors remains unknown.
最近的研究表明，在先兆子痫患者的血清中经常检测到针对血管紧张素 II 型 1 受体（AT1R-AA）的自身抗体，这表明它们可能在这种疾病的发病机制中发挥重要作用。然而，由于缺乏需要繁琐、耗时和昂贵的生物测定法来检测 AT1R-AA 的适当大型对照研究，AT1R-AA 在先兆子痫中的真正临床意义仍然存在争议。目前，尚不清楚在大量先兆子痫的墨西哥裔妇女中 AT1R-AA 的流行情况。为了阐明这一问题，我们评估了在一大群患有先兆子痫的墨西哥裔妇女中存在 AT1R-AA 的情况及其潜在的临床意义。
采用横断面设计，我们通过一种新的生物测定法在 525 名孕妇（99 名健康孕妇、96 名轻度子痫前期和 330 名重度子痫前期）中确定了 AT1R-AA 的存在，该方法使用稳定表达重组大鼠 AT1R 的人胚肾 293 细胞和 4x 激活 T 细胞核因子响应荧光素酶构建体，以及中国仓鼠卵巢（CHO）细胞的参考测定法。
我们发现，来自健康孕妇和子痫前期患者血清的 IgG 不能在表达功能性血管紧张素 II 受体 1 的 HEK-293 和中国仓鼠卵巢细胞中诱导荧光素酶活性。因此，AT1R-AA 患者的频率为零。
我们得出结论，在墨西哥裔妇女中，激动性 AT1R-AA 不能作为参与子痫前期发病机制的因素。这些发现是否归因于遗传或环境因素尚不清楚。
