Placental ABCA1 and ABCG1 expression in gestational disease: Pre-eclampsia affects ABCA1 levels in syncytiotrophoblasts

Placental ABCA1 and ABCG1 expression in gestational disease: Pre-eclampsia affects ABCA1 levels in syncytiotrophoblasts
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DOI:
10.1016/j.placenta.2013.06.309
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发表时间:
2013-11-01
期刊:
影响因子:
3.8
通讯作者:
Albrecht, C.
Albrecht, C.
中科院分区:
医学3区
文献类型:
--
作者:
Baumann, M.;Koerner, M.;Albrecht, C.

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简介:通过ATP结合盒转运体ABCA 1和ABCG 1的经胎盘的胎儿-母体脂质交换对于正常的胎儿发育是重要的。然而,只有稀缺和相互矛盾的数据存在的参与这些转运在妊娠期疾病。胎盘样品(n = 72)来源于常见的妊娠期疾病,包括先兆子痫(PE)、HELLP、宫内生长受限(IUGR)、妊娠期肝内胆汁淤积症和妊娠期糖尿病,评估其ABCA 1和ABCG 1表达水平,并与年龄匹配的对照胎盘进行qRT-PCR和免疫组织化学比较。ABCA 1的表达,另外研究了免疫印迹在胎盘膜囊泡。此外,胎盘的胆固醇和磷脂含量进行了assessed.Results:ABCA 1 mRNA水平之间的早产儿和长期控制胎盘显着差异(p = 0.0013)。与胎龄匹配的对照组相比,它们在单独的PE和PE伴IUGR中下调(分别为p = 0.0006和p = 0.0012),但在单独的IUGR、单独的HELLP和其他妊娠疾病中无变化。相应地,在PE中,ABCA 1蛋白表达在绒毛合胞体滋养层(p = 0.011)和绒毛胎儿内皮细胞(p = 0.036)的顶膜中显著降低。此外,在PE有一个显着增加的胎盘总的和个别类别的磷脂,这是部分相关的ABCA 1表达减少。相反,ABCG 1的mRNA和蛋白水平是稳定的调查conditions.Conclusions:在妊娠期疾病,有一个特定的下调胎盘ABCA 1的表达在胎儿-母亲的脂质交换在PE的网站。在功能水平上,胎盘脂质浓度的增加提供了这种疾病中ABCA 1转运能力受损的间接证据。(C)2013爱思唯尔有限公司保留所有权利。
Introduction: Transplacental feto-maternal lipid exchange through the ATP-binding cassette transporters ABCA1 and ABCG1 is important for normal fetal development. However, only scarce and conflicting data exist on the involvement of these transporters in gestational disease.Methods: Placenta samples (n = 72) derived from common gestational diseases, including pre-eclampsia (PE), HELLP, intrauterine growth restriction (IUGR), intrahepatic cholestasis of pregnancy and gestational diabetes, were assessed for their ABCA1 and ABCG1 expression levels and compared to age-matched control placentas with qRT-PCR and immunohistochemistry. ABCA1 expression was additionally investigated with immunoblot in placental membrane vesicles. Furthermore, placental cholesterol and phospholipid contents were assessed.Results: ABCA1 mRNA levels differed significantly between preterm and term control placentas (p = 0.0013). They were down-regulated in isolated PE and PE with IUGR (p = 0.0006 and p = 0.0012, respectively), but unchanged in isolated IUGR, isolated HELLP and other gestational diseases compared to gestational age-matched controls. Correspondingly, in PE, ABCA1 protein expression was significantly reduced in the apical membrane of the villous syncytiotrophoblast (p = 0.011) and in villous fetal endothelial cells (p = 0.036). Furthermore, in PE there was a significant increase in the placental content of total and individual classes of phospholipids which were partially correlated with diminished ABCA1 expression. Conversely, ABCG1 mRNA and protein levels were stable in the investigated conditions.Conclusions: In gestational disease, there is a specific down-regulation of placental ABCA1 expression at sites of feto-maternal lipid exchange in PE. At a functional level, the increase in placental lipid concentrations provides indirect evidence of an impaired transport capacity of ABCA1 in this disease. (C) 2013 Elsevier Ltd. All rights reserved.