Albrecht C, Soumian S, Tetlow N, Patel P, Sullivan M H F, Lakasing L, Nicolaides K, Williamson C
MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, UK.
Placenta. 2007 Jul;28(7):701-8. doi: 10.1016/j.placenta.2006.10.001. Epub 2006 Nov 17.
The ATP binding cassette transporter A1 (ABCA1) mediates cellular cholesterol and phospholipid efflux, and is implicated in phosphatidylserine translocation and apoptosis. Loss of functional ABCA1 in null mice results in severe placental malformation. This study aimed to establish the placental localisation of ABCA1 and to investigate whether ABCA1 expression is altered in placentas from pregnancies complicated by pre-eclampsia and antiphospholipid syndrome. ABCA1 mRNA and protein localisation studies were carried out using in situ hybridization and immunohistochemistry. Comparisons of gene expression were performed using real-time PCR and immunoblotting. ABCA1 mRNA and protein was localised to the apical syncytium of placental villi and endothelia of fetal blood vessels within the villi. ABCA1 mRNA expression was reduced in placentas from women with APS when compared to controls (p<0.001), and this was paralleled by reductions in ABCA1 protein expression. There were no differences in ABCA1 expression between placentas from pre-eclamptic pregnancies and controls. The localisation of ABCA1 in human placenta is consistent with a role in cholesterol and phospholipid transport. The decrease in ABCA1 protein in APS may reflect reduced cholesterol transport to the fetus affecting the formation of cell membranes and decreasing the level of substrate available for steroidogenesis.
ATP结合盒转运蛋白A1（ABCA1）介导细胞内胆固醇和磷脂的流出，并与磷脂酰丝氨酸转运和细胞凋亡有关。ABCA1功能缺失的基因敲除小鼠会出现严重的胎盘畸形。本研究旨在确定ABCA1在胎盘中的定位，并调查子痫前期和抗磷脂综合征合并妊娠的胎盘组织中ABCA1的表达是否发生改变。采用原位杂交和免疫组织化学方法进行ABCA1 mRNA和蛋白的定位研究。运用实时聚合酶链反应和免疫印迹法对基因表达进行比较。ABCA1 mRNA和蛋白定位于胎盘绒毛的顶端合体滋养层以及绒毛内胎儿血管的内皮细胞。与对照组相比，抗磷脂综合征患者胎盘组织中ABCA1 mRNA表达降低（p<0.001），ABCA1蛋白表达也相应减少。子痫前期妊娠胎盘组织与对照组胎盘组织中ABCA1的表达无差异。ABCA1在人胎盘中的定位与其在胆固醇和磷脂转运中的作用一致。抗磷脂综合征中ABCA1蛋白减少可能反映了胆固醇向胎儿转运减少，影响细胞膜形成，并降低了用于类固醇生成的底物水平。
