Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome
Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome
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DOI：
10.1016/j.ymgme.2008.01.015
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发表时间：
2008-06-01
影响因子：
3.8
通讯作者：
Woollett, Laura A.
中科院分区：
文献类型：
--
作者：
Jenkins, Katie T.;Merkens, Louise S.;Woollett, Laura A.
本实验室以前的研究表明，母体来源的胆固醇可以从滋养层细胞流出到胎儿HDL和血浆中。我们首次有机会研究了Smith-Lemli-Opitz综合征（SLOS）胎儿的HDL和血浆从滋养层排出胆固醇的能力。由于脂蛋白水平通常很低，尚不清楚胆固醇是否会外排至SLOS胎儿。为了回答这个问题，从SLOS胎儿和分娩后未受影响的胎儿的胎盘中收集脐带血。受影响胎儿的血浆胆固醇浓度非常低;胆固醇、7-脱氢胆固醇和8-脱氢胆固醇浓度分别为14.1、4.5和5.2 mg/dl。与未受影响的胎儿或成人的HDL相比，胎儿SLOS的HDL从滋养层细胞系中流出的胆固醇多约50%，尺寸较小，胆固醇与磷脂的比例较低。SLOS胎儿血浆中的胆固醇流出百分比与未受影响的胎儿血浆或成人血浆相似，这可能是由于之前SLOS患者中证实的HDL颗粒较少。这些新的数据表明，胆固醇缺乏的SLOS胎儿是能够从滋养层细胞中获得胆固醇的时候，胆固醇在发展中发挥着关键作用，并有影响的设计治疗胆固醇缺乏综合征，以及了解产前胆固醇转运在人类。(c)2008年爱思唯尔公司All rights reserved.
Previous studies from this laboratory have shown that maternal-derived cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the opportunity to study for the first time the ability of HDL and plasma from a fetus with the Smith-Lemli-Opitz syndrome (SLOS) to efflux cholesterol from trophoblasts. It was unclear whether cholesterol could be effluxed to fetuses with SLOS since lipoprotein levels are often very low. To answer this question, cord blood was collected from the placentas of an SLOS fetus and unaffected fetuses just after delivery. Plasma cholesterol concentrations were very low in the affected fetus; cholesterol, 7-dehydrocholesterol, and 8-dehydocholesterot concentrations were 14.1, 4.5, and 5.2 mg/dl, respectively. The HDL from the fetal SLOS effluxed approximate to 50% more cholesterol from a trophoblast cell line, were smaller in size, and had a lower cholesterol to phospholipid ratio as compared to HDL from unaffected fetuses or adults. Plasma from the SLOS fetus effluxed cholesterol to a similar percentage as unaffected fetal plasma or adult plasma, possibly due to fewer HDL particles as demonstrated in previous SLOS patients. These novel data demonstrate that the cholesterol-deficient SLOS fetus is able to obtain cholesterol from trophoblasts at a time when cholesterol is playing a critical role in development, and has implications for design of treatments for cholesterol deficiency syndromes as well as understanding of prenatal cholesterol transport in humans. (c) 2008 Elsevier Inc. All rights reserved.