Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia-a step forward but not the definitive answer
Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia-a step forward but not the definitive answer
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DOI：
10.1016/j.jri.2009.09.001
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发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Lorquet, S.
中科院分区：
文献类型：
--
作者：
Foidart, J. M.;Schaaps, J. P.;Lorquet, S.
先兆子痫。(PE)是一种妊娠特异性综合征，其特征为高血压、蛋白尿和水肿，在胎盘分娩时消退。人们认为这是由于滋养层对母体螺旋动脉的侵入不足而导致胎盘形成受损的结果。在PE中，游离血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）的母体血浆浓度降低，而可溶性fms样酪氨酸激酶-1（sFIt-1）和可溶性内皮糖蛋白（sEng）的浓度升高。这些可溶性受体可结合母体循环中的VEGF、PLGF和TGF β 1和TGF β 3，导致许多母体组织中的内皮功能障碍。因此，有一种观点认为，发病机制或多或少澄清。根据血管理论，不良的胎盘形成导致不良的子宫胎盘灌注和缺氧，其刺激sFlt-1和sEng产生，引起母体综合征。这一假设最近受到了挑战。缺氧作为sFlt-1释放的主要刺激的作用受到质疑，炎症机制的作用受到强调。根据这一炎症理论，不良的胎盘可能比缺氧更易发生胎盘氧化应激，内皮功能障碍可能是更广泛的全身性炎症疾病的一部分。最后，最近证实激活血管紧张素I受体的自身抗体在实验上在PE中发挥主要致病作用，进一步表明这种情况的病因多效性。本文旨在对近年来的假说及其对早期诊断、预防和治疗的启示进行批判性的评价。(C)2009年由Elsevier爱尔兰有限公司出版。
Preeclampsia. (PE) is a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, which resolves on placental delivery. It is thought to be the consequence of impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries. In PE the maternal plasma concentration of free vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) is decreased whereas the concentration of soluble fms-like tyrosine kinase-1 (sFIt-1) and of soluble endoglin (sEng) is increased. These soluble receptors may bind VEGF, PLGF and TGF beta 1 and TGF beta 3 in the maternal circulation, causing endothelial dysfunction in many maternal tissues. Hence there is a view that the pathogenesis is more or less clarified. According to the vascular theory, poor placentation leads to poor uteroplacental perfusion and hypoxia, which stimulates sFlt-1 and sEng production causing the maternal syndrome. This assumption has been recently challenged. The role of hypoxia as the main stimulus for release of sFlt-1 has been questioned and the role of inflammatory mechanisms has been emphasized. According to this inflammatory theory, poor placentation may predispose more to placental oxidative stress than hypoxia and endothelial dysfunction may be part of a broader disorder of systemic inflammation. Finally, the recent demonstration of activating auto-antibodies to the angiotensin I receptor that experimentally play a major pathogenic role in PE further suggests a pleiotropism of aetiologies for this condition. The purpose of this review is to critically evaluate the recent hypotheses and their possible insights on early diagnosis, prevention and treatment. (C) 2009 Published by Elsevier Ireland Ltd.