Gizurarson Sveinbjorn, Sigurdardottir Elisabet Run, Meiri Hamutal, Huppertz Berthold, Sammar Marei, Sharabi-Nov Adi, Mandalá Maurizio, Osol George
Faculty of Pharmaceutical Sciences, School of Health Science, University of Iceland, Reykjavik, Iceland.
Fetal Diagn Ther. 2016;39(1):56-63. doi: 10.1159/000381914. Epub 2015 Aug 28.
Reduced first-trimester concentrations of placental protein 13 (PP13) are associated with subsequent development of preeclampsia, a major pregnancy disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood pressure and augments expansive remodeling of the uteroplacental vasculature in pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was associated with a reversible blood pressure reduction that returned to normal on day 15. In addition, PP13 caused venous expansion that is larger in the venous branches closer to the placenta. Then, it increased placental and pup weights. Similar administration of a truncated PP13 variant (DelT221) that is unable to bind carbohydrates (a rare spontaneous mutation associated with a high frequency of severe early preeclampsia among Blacks in South Africa) produced a hypotensive effect similar to the full-length molecule, but without venous remodeling and increased placental and pup weights. These results indicate the importance of PP13 carbohydrate binding for inducing vascular remodeling and improving reproductive outcome. Future studies are needed to determine whether beneficial effects would be evident in animal models of preeclampsia or in women predisposed to the development of preeclampsia.
孕早期胎盘蛋白13（PP13）浓度降低与子痫前期（一种主要的妊娠疾病）的后续发展相关。我们之前表明，PP13具有血管舒张作用，可降低血压并增强孕鼠子宫胎盘血管系统的扩展性重塑。在本研究中，将缓释渗透泵植入妊娠大鼠（第8天）体内，以提供为期1周的PP13补充。治疗与血压可逆性降低相关，血压在第15天恢复正常。此外，PP13导致静脉扩张，在靠近胎盘的静脉分支中扩张更为明显。然后，它增加了胎盘和幼崽的重量。给予一种截短的PP13变体（DelT221，其无法结合碳水化合物，这是一种与南非黑人中严重早发型子痫前期高频率相关的罕见自发突变）进行类似给药，产生了与全长分子相似的降压作用，但没有静脉重塑，也未增加胎盘和幼崽的重量。这些结果表明PP13碳水化合物结合对于诱导血管重塑和改善生殖结局的重要性。未来需要开展研究，以确定在子痫前期动物模型或易患子痫前期的女性中是否会出现明显的有益效果。
