Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm.

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm.
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DOI:
10.1038/srep38477
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发表时间:
2016-12-09
期刊:
影响因子:
4.6
通讯作者:
Martin-Ventura JL
Martin-Ventura JL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Burillo E;Jorge I;Martínez-López D;Camafeita E;Blanco-Colio LM;Trevisan-Herraz M;Ezkurdia I;Egido J;Michel JB;Meilhac O;Vázquez J;Martin-Ventura JL

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高密度脂蛋白(HDL)是一种复杂的蛋白质和脂类组合,其组成在不同的病理情况下会发生变化。因此,对高密度脂蛋白蛋白质组的分析可以深入了解腹主动脉瘤(AAA)的主要机制,并有可能检测到新的系统生物标志物。我们对从再生障碍性贫血患者(N = 14)和对照研究参与者(N = 7)血浆中分离的HDL进行了多重定量蛋白质组学分析。验证通过蛋白质印迹(HDL)、免疫组织化学(组织)和ELISA法(血浆)进行。AAA患者高密度脂蛋白表达增加,α-2巨球蛋白和C4b结合蛋白表达降低。AAA中与高密度脂蛋白改变相关的主要途径是氧化应激和免疫炎症反应。在AAA组织中,PRDX6与中性粒细胞、血管平滑肌细胞和脂质氧化共存。此外,腹主动脉瘤患者(N = 47)血浆PrDX6水平高于对照组(N = 27),反映全身氧化应激增加。PRDX6与腹主动脉直径呈正相关。对高密度脂蛋白蛋白质组的分析表明,氧化还原失衡是AAA的主要机制,抗氧化剂PRDX6是AAA的一个新的系统生物标志物。
High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.
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