DeSousa J, Tong M, Wei J, Chamley L, Stone P, Chen Q
Maternal Fetal Medicine, Auckland City Hospital, Auckland, New Zealand.
Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand.
J Hum Hypertens. 2016 May;30(5):303-8. doi: 10.1038/jhh.2015.73. Epub 2015 Jul 9.
Preeclampsia is a disorder of pregnancy characterized by endothelial activation. It is believed to be a response to a 'toxin(s)' from the placenta including trophoblastic debris and inflammatory cytokines. Calcium is known to reduce the risk of preeclampsia but the mechanism of its protective effect remains unknown. In this study, we investigated the potential mechanism(s) of calcium supplementation for preventing endothelial activation induced by trophoblastic debris. Trophoblastic debris was harvested from preeclamptic placentae and also from first-trimester placentae, which had been treated with preeclamptic sera. Endothelial cells were then cultured with trophoblastic debris in the presence of calcium. Endothelial activation was measured by quantifying endothelial cell-surface intercellular adhesion molecule-1 (ICAM-1) and by U937 monocyte adhesion to endothelial cells. The expression of ICAM-1 and U937 adhesion to endothelial cells were significantly reduced following exposure of endothelial cells to trophoblastic debris from preeclamptic placenta or from first-trimester placentae treated with preeclamptic sera in the presence of calcium compared with treatment without calcium. The expression of ICAM-1 was also significantly reduced following exposure of endothelial cells to trophoblastic debris with the nitric oxide donor or following treatment of endothelial cells with interleukin (IL)-1β in the presence of calcium. Our study demonstrated that calcium supplementation prevented endothelial cell activation induced by trophoblastic debris from preeclamptic placentae. The nitric oxide synthase (NOS) pathway and anti-inflammatory effects are involved in the action of calcium on endothelial cell activation. These findings may suggest, at least in part, the protective mechanism of calcium supplementation on preeclampsia.
子痫前期是一种以血管内皮细胞激活为特征的妊娠疾病。它被认为是对来自胎盘的一种或多种“毒素”的反应，这些毒素包括滋养层碎片和炎性细胞因子。已知钙可降低子痫前期的风险，但其保护作用的机制尚不清楚。在本研究中，我们调查了补钙预防滋养层碎片诱导的血管内皮细胞激活的潜在机制。从子痫前期胎盘以及用子痫前期血清处理过的孕早期胎盘收集滋养层碎片。然后将内皮细胞与滋养层碎片在有钙的情况下进行培养。通过定量内皮细胞表面细胞间黏附分子-1（ICAM-1）以及U937单核细胞与内皮细胞的黏附来测量内皮细胞激活。与无钙处理相比，内皮细胞在有钙的情况下暴露于子痫前期胎盘的滋养层碎片或用子痫前期血清处理过的孕早期胎盘的滋养层碎片后，ICAM-1的表达以及U937与内皮细胞的黏附显著降低。内皮细胞在有钙的情况下暴露于含一氧化氮供体的滋养层碎片后或用白细胞介素（IL）-1β处理内皮细胞后，ICAM-1的表达也显著降低。我们的研究表明，补钙可预防子痫前期胎盘的滋养层碎片诱导的内皮细胞激活。一氧化氮合酶（NOS）途径和抗炎作用参与了钙对内皮细胞激活的作用。这些发现至少部分地提示了补钙对子痫前期的保护机制。
