Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, Graz 8010, Austria.
Hum Reprod Update. 2013 Jul-Aug;19(4):391-405. doi: 10.1093/humupd/dmt003. Epub 2013 Feb 17.
Pre-eclampsia affects 2-7% of all pregnant women and is a major cause of maternal and fetal morbidity and mortality. The etiology of pre-eclampsia is still unknown but it is well documented that impaired placentation is a major contributor to its development. One of the placenta-specific proteins is placental protein 13 (PP13). Lower first trimester levels of maternal serum PP13 and its encoding placental mRNA are associated with the development of both early and late-onset severe pre-eclampsia. In cases where this protein is mutated, the frequency of pre-eclampsia is higher.
19 out of 68 studies on PP13, published between January 2006 and September 2012, were used to evaluate the value of maternal blood PP13 as a marker of pre-eclampsia.
A meta-analysis presented in this review shows that low serum levels of PP13 in the first trimester of pregnancy can predict the development of pre-eclampsia later in pregnancy. Although some functions of this protein have been assessed in in vitro experiments, the in vivo functions of PP13 are still unknown, especially when circulating in the maternal bloodstream. A recent pilot study has shown that in gravid rats PP13 causes significant vasodilatation, reduced blood pressure and increased maternal uterine artery remodeling.
Reviewing these effects of PP13, the authors propose the use of PP13 as a new drug candidate. Replenishing PP13 in those women with low serum levels early in pregnancy may help prepare their vasculature for pregnancy. This novel pharmacological approach to combat pre-eclampsia is presented as a new direction to transfer from individualized risk to personalized prevention.
子痫前期影响所有孕妇的 2-7%,是孕产妇和胎儿发病率和死亡率的主要原因。子痫前期的病因尚不清楚,但有大量文献记载,胎盘功能障碍是其发展的主要原因之一。胎盘蛋白 13(PP13)是胎盘特有的蛋白之一。母血清中 PP13 及其编码的胎盘 mRNA 在孕早期水平降低与早发和晚发重度子痫前期的发展有关。在这种蛋白质发生突变的情况下,子痫前期的发病率更高。
在 2006 年 1 月至 2012 年 9 月期间发表的 68 项关于 PP13 的研究中,有 19 项用于评估母体血液 PP13 作为子痫前期标志物的价值。
本综述中的荟萃分析表明,妊娠早期血清 PP13 水平低可预测妊娠后期子痫前期的发生。尽管已经在体外实验中评估了这种蛋白质的一些功能,但 PP13 的体内功能仍不清楚,尤其是在母体血液循环中。最近的一项初步研究表明,在妊娠大鼠中,PP13 可引起明显的血管舒张、血压降低和母体子宫动脉重塑增加。
回顾 PP13 的这些作用,作者提出将 PP13 用作新药候选物。在妊娠早期母体血清水平较低的女性中补充 PP13 可能有助于为其血管系统做好妊娠准备。这种针对子痫前期的新型药物治疗方法被提出作为从个体化风险向个体化预防转移的新方向。