Abstract：
As one of the leading causes of premature birth and maternal and infant mortality worldwide, preeclampsia remains a major unmet public health challenge. Preeclampsia and related hypertensive disorders of pregnancy are estimated to cause >75 000 maternal and 500 000 infant deaths globally each year. Because of rising rates of risk factors such as obesity, in vitro fertilization and advanced maternal age, the incidence of preeclampsia is going up with rates ranging from 5% to 10% of all pregnancies worldwide. A major discovery in the field was the realization that the clinical phenotypes related to preeclampsia, such as hypertension, proteinuria, and other adverse maternal/fetal events, are due to excess circulating soluble fms-like tyrosine kinase-1 (sFlt-1, also referred to as sVEGFR-1). sFlt-1 is an endogenous anti-angiogenic protein that is made by the placenta and acts by neutralizing the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). During the last decade, this work has spawned a new era of molecular diagnostics for early detection of this condition. Antagonizing sFlt-1 either by reducing production or blocking its actions has shown salutary effects in animal models. Further, in early-stage human studies, the therapeutic removal of sFlt-1 from maternal circulation has shown promise in delaying disease progression and improving outcomes. Recently, the FDA approved the first molecular test for preterm preeclampsia (sFlt-1/PlGF ratio) for clinical use in the United States. Measuring serum sFlt-1/PlGF ratio in the acute hospital setting may aid short-term management, particularly regarding step-up or step-down of care, decision to transfer to settings better equipped to manage both the mother and the preterm neonate, appropriate timing of administration of steroids and magnesium sulfate, and in expectant management decisions. The test itself has the potential to save lives. Furthermore, the availability of a molecular test that correlates with adverse outcomes has set the stage for interventional clinical trials testing treatments for this disorder. In this review, we will discuss the role of circulating sFlt-1 and related factors in the pathogenesis of preeclampsia and specifically how this discovery is leading to concrete advances in the care of women with preeclampsia.
摘要：
作为全球早产和母婴死亡的主要原因之一，先兆子痫仍然是一个尚未解决的重大公共卫生挑战。据估计，全球每年先兆子痫和相关的妊娠高血压疾病导致>75000名孕产妇和50000名婴儿死亡。由于肥胖等危险因素的发病率上升，体外受精和高龄产妇，先兆子痫的发病率正在上升，在全世界所有妊娠中，发病率从5%到10%不等。该领域的一个重大发现是认识到临床表型与先兆子痫有关，比如高血压，蛋白尿,和其他不良的母体/胎儿事件，是由于过量的循环可溶性fms样酪氨酸激酶-1(sFlt-1,也称为sVEGFR-1)。sFlt-1是一种内源性抗血管生成蛋白，由胎盘产生，通过中和促血管生成蛋白血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）发挥作用。在过去的十年里，这项工作催生了早期发现这种情况的分子诊断的新时代。通过减少产生或阻断其作用来拮抗sFlt-1已在动物模型中显示出有益的作用。Further,在早期人类研究中，从母体循环中治疗性去除sFlt-1在延缓疾病进展和改善结局方面显示出希望.最近,FDA批准了第一个在美国临床使用的早产先兆子痫分子检测方法(sFlt-1/PlGF比值).在急性医院环境中测量血清sFlt-1/PlGF比率可能有助于短期管理，特别是关于加强或降低护理，决定转移到更有能力管理母亲和早产新生儿的环境，服用类固醇和硫酸镁的适当时机，以及预期的管理决策。测试本身具有挽救生命的潜力。此外，与不良结局相关的分子检测的可用性为该疾病的介入临床试验奠定了基础.在这次审查中,我们将讨论循环sFlt-1和相关因素在先兆子痫发病机制中的作用,特别是这一发现如何导致先兆子痫妇女护理的具体进展.
