The BPH/5 Mouse Model of Superimposed Preeclampsia Is Not a Model of HELLP Syndrome.
The BPH/5 Mouse Model of Superimposed Preeclampsia Is Not a Model of HELLP Syndrome.
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DOI：
10.3390/biology10111179
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发表时间：
2021-11-14
期刊：
影响因子：
4.2
通讯作者：
Sones JL
中科院分区：
文献类型：
--
作者：
Johnston AN;Batts TL;Langohr IM;Moeller C;Liu CC;Sones JL
高达20%的严重子痫前期妇女出现HELLP综合征(溶血（H)，肝转氨酶升高（EL），血小板低（LP））。胎盘发育中断是导致子痫前期和HELLP综合征的原因，但为什么HELLP综合征在一些妇女中发生尚不清楚。目前还没有针对这种毁灭性疾病的靶向治疗方法，因此开发临床前模型势在必行。因此，我们试图确定血压高亚碱5 （BPH/5）小鼠，一种自发性子痫前期模型，是否也可以作为HELLP综合征的模型。尽管在妊娠期BPH/5小鼠中未发现贫血、血小板减少和肝功能障碍的血浆标志物，排除了其作为与HELLP综合征相关的PE模型的可能性，但发现了进行性脂肪肝表型。BPH/5小鼠可作为叠加性子痫前期肝脂肪变性的模型。子痫前期（PE）是一种多系统的妊娠疾病，影响全世界2-8%的妇女。pe引起的肝病是一种罕见但重要的妊娠并发症。PE患者肝功能障碍的发病机制尚不清楚，但与胎盘发育早期血管生成异常、炎症和缺氧事件有关。由于BPH/5小鼠在妊娠期间出现了PE的母体和胎儿特征，我们假设它们也可能具有人类PE相关溶血升高肝转氨酶低血小板（HELLP）综合征的临床病理表现。使用该模型，我们确定微血管病性溶血、血小板减少症和肝酶升高不会发生在妊娠中后期。怀孕的BPH/5小鼠没有肝脏炎症的组织学证据，但它们在孕前和妊娠中后期的微脂肪变性评分确实增加，并在妊娠后期的一小部分小鼠中进展为大脂肪变性。TNF-α、CXCL-10和TLR-2的转录上调发生在大脂肪变性发病前的妊娠中期。BPH/5雌性小鼠不是HELLP综合征的模型，但可能是与妊娠相关的脂肪肝疾病的模型。
HELLP syndrome ((H) for hemolysis, (EL) for elevated liver transaminases, and (LP) for low platelets) occurs in up to 20% of women with severe preeclampsia. Disrupted placental development is causal to both preeclampsia and HELLP syndrome, yet why HELLP syndrome develops in some women remains unclear. Targeted treatments for this devastating disease are currently unavailable, and the development of preclinical models is imperative. Therefore, we sought to determine whether the blood pressure high subline 5 (BPH/5) mouse, a spontaneous model of preeclampsia, could also serve as a model of HELLP syndrome. Although anemia, thrombocytopenia, and plasma markers of liver dysfunction were not found in the BPH/5 mouse during pregnancy, precluding it as a model of PE associated with HELLP syndrome, a progressive fatty liver phenotype was identified. The BPH/5 mouse may be useful as a model of hepatic steatosis in superimposed preeclampsia. Preeclampsia (PE) is a multisystemic disease of pregnancy affecting 2–8% of women worldwide. PE-induced liver disease is a rare but important complication of pregnancy. The pathogenesis of liver dysfunction in PE is poorly understood, but is correlated with dysregulated angiogenic, inflammatory, and hypoxic events in the early phase of placental development. Because BPH/5 mice develop the maternal and fetal hallmarks of PE during pregnancy, we hypothesized that they may also share the clinicopathologic findings of the human PE-associated hemolysis elevated liver transaminases low platelets (HELLP) syndrome. Using this model, we determined that microangiopathic hemolysis, thrombocytopenia, and elevated liver enzymes do not occur in mid to late gestation. Pregnant BPH/5 mice do not develop histologic evidence of hepatic inflammation, but they do have increased microsteatosis scores at preconception and in mid to late gestation that progress to macrosteatosis in a subset of mice in late gestation. The transcriptional upregulation of TNF-α, CXCL-10, and TLR-2 occurs in mid gestation prior to the onset of macrosteatosis. The BPH/5 female mouse is not a model of HELLP syndrome, but may be a model of fatty liver disease associated with pregnancy.
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影响因子：
4.6
作者：
Reijnders, Dorien;Liu, Chin-Chi;Sones, Jenny L.
通讯作者：
Sones, Jenny L.
影响因子：
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作者：
Oe Y;Ko M;Fushima T;Sato E;Karumanchi SA;Sato H;Sugawara J;Ito S;Takahashi N
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影响因子：
8.3
作者：
Davisson, RL;Hoffmann, DS;Bates, JN
通讯作者：
Bates, JN
影响因子：
3.7
作者：
Liang W;Menke AL;Driessen A;Koek GH;Lindeman JH;Stoop R;Havekes LM;Kleemann R;van den Hoek AM
通讯作者：
van den Hoek AM
DOI：
10.1152/ajpregu.00334.2018
发表时间：
2019-07-01
影响因子：
2.8
作者：
Reijnders, Dorien;Olson, Kelsey N.;Sones, Jenny L.
通讯作者：
Sones, Jenny L.