Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand; The Hospital of Obstetrics & Gynaecology, Fudan University, China; Wuxi Maternity and Child Health Hospital, Nanjing Medical University, China.
Placenta. 2013 Dec;34(12):1196-201. doi: 10.1016/j.placenta.2013.09.014. Epub 2013 Sep 28.
A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to "toxins" from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and others include inflammatory cytokines. Calcium supplementation appears to protect "at-risk" women from developing preeclampsia by an unknown mechanism. In this study we investigate whether the addition of high levels of calcium to endothelial cells prior to their exposure to the preeclampsia-associated activators could reduce the endothelial cell activation.
NTD was harvested from 1st trimester placental explants. Endothelial cells were treated with varied concentrations of calcium prior to exposure to NTD, IL-6 or preeclamptic sera or low levels of calcium. Activation was monitored by quantifying endothelial cell-surface ICAM-1 by ELISA or U937 adhesion to endothelial cells. The activity of endothelial cell nitric oxide synthetase was blocked with L-NAME.
Pre-treatment with increasing concentrations of calcium inhibited the activation of endothelial cells in response to NTD or IL-6 or preeclamptic sera. Inhibiting nitric oxide synthetase, using L-NAME, reduced the ability of high calcium levels to protect endothelial cell activation. Pre-treatment with calcium did not prevent endothelial cell activation induced by the reduction of the levels of calcium but additional calcium treatment did prevent endothelial cell activation induced by low calcium.
Our results demonstrate calcium supplementation may prevent the activation of the endothelium in response to activators. These results may partially explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in vitro mechanistic support for the use of calcium supplementation in at-risk women.
子痫前期的一个标志是内皮细胞功能障碍/激活，以响应来自胎盘的“毒素”。坏死的滋养层碎片（NTD）是一种可能的胎盘毒素，其他包括炎症细胞因子。钙补充似乎通过未知机制保护“高危”妇女免于发生子痫前期。在这项研究中，我们研究了在暴露于与子痫前期相关的激活剂之前，向内皮细胞中添加高水平的钙是否可以减少内皮细胞的激活。
从 1 期胎盘外植体中收获 NTD。在暴露于 NTD、IL-6 或子痫前期血清或低水平钙之前，用不同浓度的钙处理内皮细胞。通过 ELISA 或 U937 与内皮细胞的黏附来定量内皮细胞表面 ICAM-1 来监测激活。用 L-NAME 阻断内皮细胞一氧化氮合酶的活性。
用递增浓度的钙预处理可抑制内皮细胞对 NTD 或 IL-6 或子痫前期血清的激活。用 L-NAME 抑制一氧化氮合酶可降低高钙水平保护内皮细胞激活的能力。钙预处理不能预防由钙水平降低引起的内皮细胞激活，但额外的钙处理可预防由低钙引起的内皮细胞激活。
我们的结果表明，钙补充可能预防内皮细胞对激活剂的激活。这些结果部分解释了钙补充在降低子痫前期风险方面的益处，并为高危妇女使用钙补充提供了体外机制支持。
