Interferon-α and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia.
Interferon-α and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia.
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DOI：
10.1002/art.39029
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发表时间：
2015-04
影响因子：
13.3
通讯作者：
Salmon, Jane E.
中科院分区：
文献类型：
--
作者：
Andrade, Danieli;Kim, Mimi;Blanco, Luz P.;Karumanchi, S. Ananth;Koo, Gloria C.;Redecha, Patricia;Kirou, Kyriakos;Alvarez, Angela M.;Mulla, Melissa J.;Crow, Mary K.;Abrahams, Vikki M.;Kaplan, Mariana J.;Salmon, Jane E.
研究妊娠早期IFN-α升高是否与不良妊娠结局相关，并检查其与血管生成失衡的关系。妇女参加了狼疮妊娠的病例对照纵向研究。每月采集妊娠期血清样本，测定IFN-α、抗血管生成因子sFlt 1和促血管生成因子（PlGF）。将28例妊娠结局不良的SLE患者分别与1例妊娠无并发症的SLE患者和1例妊娠健康对照组进行配对。评估IFN-α和/或sFlt1对人内皮细胞和内皮-滋养层相互作用的影响。与无并发症妊娠的SLE患者相比，先兆子痫患者在出现临床症状前IFN-α水平升高。非自身免疫性子痫前期患者IFN-α水平没有升高。在低IFN-α的SLE患者中，显著的血管生成失衡（较高的sFlt1、较低的PlGF和较高的sFlt1/PlGF比值）先于先兆子痫的母体表现，而在高IFN-α的SLE患者中，先兆子痫的发生没有全身性血管生成失衡的证据。用sFlt1处理人内皮细胞可诱导sFlt1 mRNA的表达，IFN-α显著增强对sFlt1的反应。在螺旋动脉转化模型中，只有IFN-α和sFlt1一起破坏滋养层细胞重塑内皮管结构的能力。我们的研究确定了IFN-α诱导抗血管生成环境的新机制，增加了内皮细胞对sFlt1的敏感性，并表明IFN-α升高可能有助于某些SLE妊娠中先兆子痫的发病机制。
To investigate whether elevated IFN-α early in pregnancy is associated with poor pregnancy outcomes and examine its relationship to angiogenic imbalance. Women were enrolled in a case-control longitudinal study of lupus pregnancies. Serum samples obtained monthly through pregnancy were assayed for IFN-α and for antiangiogenic factor, sFlt1, and proangiogenic factor, (PlGF). Each of 28 SLE patients with poor pregnancy outcome was matched to an SLE patient with an uncomplicated pregnancy and to a pregnant healthy control. The effects of IFN-α and/or sFlt1 on-human endothelial cells and endothelial-trophoblast interactions was assessed. Compared to SLE patients with uncomplicated pregnancies, patients with preeclampsia had increased IFN-α before clinical symptoms. Non-autoimmune patients destined for preeclampsia did not have increased IFN-α. In SLE patients with low IFN-α, marked angiogenic imbalance (higher sFlt1, lower PlGF and higher sFlt1/PlGF ratios) precedes maternal manifestations of preeclampsia, whereas in SLE with high IFN-α, preeclampsia occurs without evidence of systemic angiogenic imbalance. Treatment of human endothelial cells with sFlt1 induced expression of sFlt1 mRNA, and IFN-α dramatically amplified responses to sFlt1. In a model of spiral artery transformation, only IFN-α and sFlt1 together disrupted the ability of trophoblast cells to remodel endothelial tube structures. Our studies identify a new mechanism by which IFN-α induces an antiangiogenic milieu, increases the sensitivity of endothelial cells to sFlt1, and suggest that elevated IFN-α may contribute to pathogenesis of preeclampsia in some SLE pregnancies.
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干扰素-α：系统性红斑狼疮的治疗靶点。
影响因子：
2.3
作者：
Crow, Mary K.
通讯作者：
Crow, Mary K.
影响因子：
2.6
作者：
JULKUNEN, H;JOUHIKAINEN, T;FRIMAN, C
通讯作者：
FRIMAN, C
影响因子：
158.5
作者：
Eremina, Vera;Jefferson, J. Ashley;Quaggin, Susan E.
通讯作者：
Quaggin, Susan E.
DOI：
10.1084/jem.20130295
发表时间：
2014-01-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cotechini T;Komisarenko M;Sperou A;Macdonald-Goodfellow S;Adams MA;Graham CH
通讯作者：
Graham CH
影响因子：
10.8
作者：
Cindrova-Davies T;Sanders DA;Burton GJ;Charnock-Jones DS
通讯作者：
Charnock-Jones DS