A proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between a predisposition to preeclampsia and cardiovascular disease
A proteomic approach identifies early pregnancy biomarkers for preeclampsia: Novel linkages between a predisposition to preeclampsia and cardiovascular disease
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DOI：
10.1002/pmic.200800625
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发表时间：
2009-06-01
期刊：
影响因子：
3.4
通讯作者：
North, Robyn A.
中科院分区：
文献类型：
--
作者：
Blumenstein, Marion;McMaster, Michael T.;North, Robyn A.
先兆子痫（PE）是一种常见的、可能危及生命的妊娠综合征，由胎盘因子释放到母体循环中引发，导致母体血管功能障碍以及激活的炎症和凝血。目前没有针对PE的筛查测试。我们试图鉴定随后发生PE的女性中差异表达的血浆蛋白，这些蛋白可以作为预测生物标志物。在七项 DIGE 实验中，我们将后来患 PE 且出生体重适合胎龄婴儿 (n = 27) 或小于胎龄婴儿 (n = 12) 的女性与妊娠无并发症的健康对照 (n = 57) 的妊娠 20 周时的血浆蛋白质组进行了比较。在与适合胎龄的 PE、小于胎龄的 PE 或两者 (p90%) 相关的 49 个差异表达点中，确定了有发生 PE 风险的女性。免疫印迹证实PE前血浆中纤维蛋白原γ链和α-1-抗胰凝乳蛋白酶过度表达。鉴定出的蛋白质涉及脂质代谢、凝血、补体调节、细胞外基质重塑、蛋白酶抑制剂活性和急性期反应，表明参与PE发病机制的途径之间存在新的协同作用。我们的研究结果与最近发现的与高密度脂蛋白复合并与心血管疾病相关的蛋白质非常相似。
Preeclampsia (PE) is a common, potentially life-threatening pregnancy syndrome triggered by placental factors released into the maternal circulation, resulting in maternal vascular dysfunction along with activated inflammation and coagulation. Currently there is no screening test for PE. We sought to identify differentially expressed plasma proteins in women who subsequently develop PE that may perform as predictive biomarkers. In seven DIGE experiments, we compared the plasma proteome at 20wk gestation in women who later developed PE with an appropriate birth weight for gestational age baby (n = 27) or a small for gestational age baby (n = 12) to healthy controls with uncomplicated pregnancies (n = 57). Of the 49 differentially expressed spots associated with PE-appropriate for gestational age, PE-small for gestational age or both (p90%) classified women at risk of developing PE were identified. Immunoblots confirmed the overexpression of fibrinogen gamma chain and alpha-1-antichymotrypsin in plasma prior to PE. The proteins identified are involved in lipid metabolism, coagulation, complement regulation, extracellular matrix remodeling, protease inhibitor activity and acute-phase responses, indicating novel synergism between pathways involved in the pathogenesis of PE. Our findings are remarkably similar to recently identified proteins complexed to high-density lipoprotein and linked to cardiovascular disease.