Tjoa May Lee, Levine Richard J, Karumanchi S Ananth
Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Front Biosci. 2007 Jan 1;12:2395-402. doi: 10.2741/2241.
Preeclampsia is a major cause of maternal and neonatal morbidity and mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, hypertension and proteinuria, may be due to an excess of circulating anti-angiogenic growth factors, most notably soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng). sFlt1 is an endogenous protein that is produced by the placenta. sFlt1 is able to bind to the angiogenic growth factors vascular endothelial growth factor and placental growth factor, thereby neutralizing their functions. High serum concentrations of sFlt1 and low concentrations of free vascular endothelial growth factor and free placental growth factor have been observed during and prior to clinical manifestation of preeclampsia. More recently, serum levels of sEng were also shown to be significantly elevated in preeclamptic women and levels of sEng correlated strongly with disease severity. Therefore, measurement of sFlt1 and sEng in the maternal circulation may be a useful diagnostic and screening tool for preeclampsia. The availability of such a test to predict preeclampsia would have significant impact on current obstetrical care and may help reduce preeclampsia-induced morbidity and mortality. This review will focus on the role of angiogenic factors in normal and abnormal placental development and indicate how measurement of circulating angiogenic factors may help identify women at risk of preeclampsia.
子痫前期是全球孕产妇和新生儿发病及死亡的主要原因。尽管子痫前期的病因仍不清楚,但最近的研究表明,其主要表型,即高血压和蛋白尿,可能是由于循环中抗血管生成生长因子过多所致,最显著的是可溶性fms样酪氨酸激酶1(sFlt1)和可溶性内皮糖蛋白(sEng)。sFlt1是一种由胎盘产生的内源性蛋白质。sFlt1能够与血管生成生长因子血管内皮生长因子和胎盘生长因子结合,从而中和它们的功能。在子痫前期临床表现期间及之前,已观察到血清中sFlt1浓度高,而游离血管内皮生长因子和游离胎盘生长因子浓度低。最近,子痫前期妇女的血清sEng水平也显示显著升高,且sEng水平与疾病严重程度密切相关。因此,检测母体循环中的sFlt1和sEng可能是子痫前期有用的诊断和筛查工具。这样一种预测子痫前期的检测方法的出现将对当前的产科护理产生重大影响,并可能有助于降低子痫前期所致的发病率和死亡率。本综述将重点关注血管生成因子在正常和异常胎盘发育中的作用,并指出检测循环血管生成因子如何有助于识别子痫前期风险女性。