Identification of Peroxiredoxin-1 as a Novel Biomarker of Abdominal Aortic Aneurysm
Identification of Peroxiredoxin-1 as a Novel Biomarker of Abdominal Aortic Aneurysm
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DOI：
10.1161/atvbaha.110.214429
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发表时间：
2011-04-01
影响因子：
8.7
通讯作者：
Martin-Ventura, Jose L.
中科院分区：
文献类型：
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作者：
Martinez-Pinna, Roxana;Ramos-Mozo, Priscila;Martin-Ventura, Jose L.
在寻找腹主动脉瘤（AAA）进展的新生物标志物中，通过差异蛋白质组学方法分析了腔内血栓（ILT）释放的蛋白质。方法和结果孵育AAA的ILT的不同层（管腔/近管腔），并通过二维差异凝胶电泳分析释放的蛋白质。通过质谱鉴定了几种参与AAA主要病理机制（蛋白水解、氧化应激和血栓形成）的差异表达蛋白。在所鉴定的蛋白质中，与ILT的近腔层相比，腔层更多地释放过氧化物氧还蛋白-1（PRX-1），这通过Western印迹、ELISA和免疫组织化学进一步验证。我们证明了AAA患者与健康受试者相比PRX-1血清水平升高，PRX-1与AAA直径、纤溶酶-抗纤溶酶和髓过氧化物酶水平呈正相关。最后，一项前瞻性研究显示PRX-1血清水平与AAA扩张率呈正相关。此外，PRX-1和AAA大小的组合有显着的附加值在预测growth.Conclusion-several蛋白质与AAA发病机制已被确定通过蛋白质组学方法在ILT条件培养基。其中，PRX-1血清水平在AAA患者中升高，并与AAA大小和生长速率相关，表明PRX-1作为AAA演变的生物标志物的潜在用途。（Arterioscler Thromb Vasc Biol.2011; 31：935 - 943.）
Objective-In the search of novel biomarkers of abdominal aortic aneurysm (AAA) progression, proteins released by intraluminal thrombus (ILT) were analyzed by a differential proteomic approach.Methods and Results-Different layers (luminal/abluminal) of the ILT of AAA were incubated, and the proteins released were analyzed by 2-dimensional difference in-gel electrophoresis. Several differentially expressed proteins involved in main AAA pathological mechanisms (proteolysis, oxidative stress, and thrombosis) were identified by mass spectrometry. Among the proteins identified, peroxiredoxin-1 (PRX-1) was more released by the luminal layer compared with the abluminal layer of the ILT, which was further validated by Western blot, ELISA, and immunohistochemistry. We demonstrated increased PRX-1 serum levels in AAA patients compared with healthy subjects and also positive correlation among PRX-1 and AAA diameter, plasmin-antiplasmin, and myeloperoxidase levels. Finally, a prospective study revealed a positive correlation between PRX-1 serum levels and AAA expansion rate. Moreover, the combination of PRX-1 and AAA size had significantly additive value in predicting growth.Conclusion-Several proteins associated with AAA pathogenesis have been identified by a proteomic approach in ILT-conditioned medium. Among them, PRX-1 serum levels are increased in AAA patients and correlate with AAA size and growth rate, suggesting the potential use of PRX-1 as a biomarker for AAA evolution. (Arterioscler Thromb Vasc Biol. 2011;31:935-943.)