Neutralization of FasL is linked to suppression of hypertension, placental inflammation, and endothelin system activation in an animal model of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. During HELLP syndrome the placenta has been reported to serve as the primary source of Fas ligand (FasL), which has an impact on inflammation and hypertension during pregnancy and is dysregulated in women with severe preeclampsia and HELLP syndrome. We hypothesize that neutralization of FasL during pregnancy in an animal model of HELLP syndrome decreases inflammation and placental apoptosis, improves endothelial damage, and improves hypertension. On gestational day (GD) 12, rats were chronically infused with placental antiangiogenic factors sFlt-1 and sEng to induce HELLP syndrome. To neutralize FasL, MFL4 or FasL antibody was infused into a subset of HELLP or normal pregnant rats on GD13. IgG infusion into another group of NP and HELLP rats on GD13 was used as a control for FasL antibody, and all rats were euthanized on GD19 after blood pressure measurement. Plasma and placentas were collected to assess inflammation, apoptosis, and the degree of placental debris activation of endothelial cells. Administration of MFL4 to HELLP rats significantly decreased blood pressure compared with untreated HELLP rats and HELLP rats infused with IgG and improved the biochemistry of HELLP syndrome. Both circulating and placental FasL were significantly attenuated in response to MFL4 infusion, as were levels of placental and circulating TNFα when compared with untreated HELLP rats and HELLP rats infused with IgG. Endothelial cells exposed to placental debris and media from HP + MFL4 rats secreted significantly less endothelin-1 compared with stimulated endothelial cells from HELLP placentas. Neutralization of FasL is associated with decreased MAP and improvement in placental inflammation and endothelial damage in an animal model of HELLP syndrome.

中文翻译：

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Fas 配体中和可减轻 HELLP 综合征动物模型中的高血压、内皮素-1 和胎盘炎症。

在溶血、肝酶升高、低血小板 (HELLP) 综合征的动物模型中，FasL 的中和与抑制高血压、胎盘炎症和内皮素系统激活有关。据报道，在 HELLP 综合征期间，胎盘是 Fas 配体 (FasL) 的主要来源，FasL 对怀孕期间的炎症和高血压有影响，并且在患有严重先兆子痫和 HELLP 综合征的女性中失调。我们假设妊娠期间在 HELLP 综合征动物模型中中和 FasL 可减少炎症和胎盘细胞凋亡，改善内皮损伤并改善高血压。在妊娠第 12 天 (GD)，大鼠长期注入胎盘抗血管生成因子 sFlt-1 和 sEng 以诱导 HELLP 综合征。为了中和 FasL，MFL4 或 FasL 抗体在 GD13 上被注入 HELLP 或正常怀孕大鼠的子集。在GD13上将IgG输注到另一组NP和HELLP大鼠中用作FasL抗体的对照，并且在血压测量后在GD19上对所有大鼠实施安乐死。收集血浆和胎盘以评估炎症、细胞凋亡和内皮细胞的胎盘碎片活化程度。与未治疗的 HELLP 大鼠和注入 IgG 的 HELLP 大鼠相比，向 HELLP 大鼠施用 MFL4 可显着降低血压，并改善 HELLP 综合征的生物化学。与未治疗的 HELLP 大鼠和输注 IgG 的 HELLP 大鼠相比，循环和胎盘 FasL 均显着减弱，以响应 MFL4 输注，胎盘和循环 TNFα 的水平也是如此。与来自 HELLP 胎盘的刺激内皮细胞相比，暴露于来自 HP + MFL4 大鼠的胎盘碎片和培养基的内皮细胞分泌的内皮素 1 显着减少。在 HELLP 综合征动物模型中，FasL 的中和与 MAP 降低以及胎盘炎症和内皮损伤的改善有关。