Palmer Kirsten
Department of Obstetrics and Gynecology, School of Clinical Sciences, Monash University, Level 5, 246 Clayton Rd, Clayton, 3168, VIC, Australia.
Methods Mol Biol. 2018;1710:27-37. doi: 10.1007/978-1-4939-7498-6_3.
Preeclampsia is a common obstetric complication globally responsible for a significant burden of maternal and perinatal morbidity and mortality. The anti-angiogenic protein, sFLT-1, plays a central role in its pathophysiology. sFLT-1 is released from a range of tissues into the circulation, where it antagonizes the activity of vascular endothelial growth factor and placental growth factor leading to endothelial dysfunction. The resulting widespread endothelial dysfunction produces the clinical features of preeclampsia including hypertension and proteinuria. Multiple splice variants of sFLT-1 have been identified, with one, known as sFLT-1 e15a, present only in humans and higher-order primates. This sFLT-1 variant is also the main form of sFLT-1 produced by the placenta. Recent work has shown that sFLT-1 e15a is significantly elevated in the placenta and circulation of women with preeclampsia. It is also biologically active, capable of causing endothelial dysfunction and end-organ dysfunction seen in preeclampsia. Indeed, overexpression of sFLT-1 e15a in mice recapitulates the preeclamptic phenotype in pregnancy. No commercial assay currently exists to analyze sFLT-1 e15a protein levels. Here, a new ELISA method to determine circulating sFLT-1 variant levels is described.
子痫前期是一种常见的产科并发症，在全球范围内导致了孕产妇和围产期发病及死亡的重大负担。抗血管生成蛋白sFLT-1在其病理生理学中起核心作用。sFLT-1从一系列组织释放到循环中，在那里它拮抗血管内皮生长因子和胎盘生长因子的活性，导致内皮功能障碍。由此产生的广泛内皮功能障碍产生了子痫前期的临床特征，包括高血压和蛋白尿。已鉴定出sFLT-1的多种剪接变体，其中一种称为sFLT-1 e15a，仅存在于人类和高等灵长类动物中。这种sFLT-1变体也是胎盘产生的sFLT-1的主要形式。最近的研究表明，子痫前期女性的胎盘和循环中sFLT-1 e15a显著升高。它也具有生物活性，能够导致子痫前期所见的内皮功能障碍和终末器官功能障碍。事实上，在小鼠中过表达sFLT-1 e15a可重现妊娠子痫前期表型。目前尚无商业检测方法来分析sFLT-1 e15a蛋白水平。在此，描述了一种测定循环sFLT-1变体水平的新ELISA方法。
