Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta.
Vitamin D prevents endothelial progenitor cell dysfunction induced by sera from women with preeclampsia or conditioned media from hypoxic placenta.
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DOI：
10.1371/journal.pone.0098527
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
von Versen-Höynck F
中科院分区：
文献类型：
--
作者：
Brodowski L;Burlakov J;Myerski AC;von Kaisenberg CS;Grundmann M;Hubel CA;von Versen-Höynck F
胎盘来源的循环因子有助于子痫前期母体内皮功能障碍。内皮集落形成细胞（ECFC）是内皮祖细胞（EPCs）的一个亚群，被认为参与血管发生和内皮修复。维生素D浓度低与子痫前期风险增加有关。我们假设，人胎儿ecfc在培养中的功能可能会被暴露于子痫前期相关因素（子痫前期血清或低氧胎盘条件培养基）所抑制，而维生素d会逆转这种抑制方式。将外植体培养的无并发症妊娠绒毛胎盘分别暴露于2%（低氧）、8%（常氧）或21%（高氧）O2中48小时，之后收集条件培养基（CM）。ECFC小管形成（Matrigel试验）和迁移是在子痫前期病例或无并发症妊娠对照的母体血清中，或在存在或不存在125 (OH)2维生素D3的情况下进行的。1,25(OH)2维生素D3逆转了子痫前期血清或缺氧胎盘CM对ecfc毛细血管形成和迁移的不利影响。通过VDR siRNA、VDR阻断或VEGF通路阻断来沉默VDR表达可降低ECFC的功能能力。维生素D可部分预防VDR或VEGF阻断的影响。维生素D可促进培养物中ecfc的毛细血管样小管形成和迁移，将暴露于子痫前期相关因素的负面影响降至最低。进一步评估维生素D在ECFC调节和子痫前期的作用是必要的。
Placenta-derived circulating factors contribute to the maternal endothelial dysfunction underlying preeclampsia. Endothelial colony forming cells (ECFC), a sub-population of endothelial progenitor cells (EPCs), are thought to be involved in vasculogenesis and endothelial repair. Low vitamin D concentrations are associated with an increased risk for preeclampsia. We hypothesized that the function of human fetal ECFCs in culture would be suppressed by exposure to preeclampsia-related factors–preeclampsia serum or hypoxic placental conditioned medium– in a fashion reversed by vitamin D. ECFCs were isolated from cord blood of uncomplicated pregnancies and expanded in culture. Uncomplicated pregnancy villous placenta in explant culture were exposed to either 2% (hypoxic), 8% (normoxic) or 21% (hyperoxic) O2 for 48 h, after which the conditioned media (CM) was collected. ECFC tubule formation (Matrigel assay) and migration were examined in the presence of either maternal serum from preeclampsia cases or uncomplicated pregnancy controls, or pooled CM, in the presence or absence of 1,25(OH)2 vitamin D3. 1,25(OH)2 vitamin D3 reversed the adverse effects of preeclampsia serum or CM from hypoxic placenta on ECFCs capillary-tube formation and migration. Silencing of VDR expression by VDR siRNA, VDR blockade, or VEGF pathway blockade reduced ECFC functional abilities. Effects of VDR or VEGF blockade were partially prevented by vitamin D. Vitamin D promotes the capillary-like tubule formation and migration of ECFCs in culture, minimizing the negative effects of exposure to preeclampsia-related factors. Further evaluation of the role of vitamin D in ECFC regulation and preeclampsia is warranted.