Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.
Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.
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DOI：
10.1371/journal.pone.0117169
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chiou SH
中科院分区：
文献类型：
--
作者：
Lee MY;Huang CH;Kuo CJ;Lin CL;Lai WT;Chiou SH
炎症在冠状动脉疾病（CAD）和动脉粥样硬化的其他表现中起关键作用。近年来，尿蛋白被发现是反映不同器官炎症状态的有用标志物。为了鉴定用于诊断CAD的潜在生物标志物，我们进行了一维SDS-凝胶电泳，然后进行了液相色谱-串联质谱（LC-MS/MS）。在尿液样本中差异表达的蛋白质中，发现单核细胞抗原CD 14在CAD患者中的表达量始终高于正常对照组。采用酶联免疫吸附法检测73例多支及单支冠状动脉病变患者尿及血清中CD 14的含量，结果显示：73例多支及单支冠状动脉病变患者尿中CD 14的含量均显著高于35例正常对照组（P < 0.001）。Logistic回归分析进一步显示，校正潜在混杂因素后，尿CD 14浓度水平与病变血管的严重程度或数量以及SYNTAX评分相关。同时，冠心病患者尿中CD 14+单核细胞比例（59.7 ± 3.6%）显著高于健康对照组（14.9 ± 2.1%）（P < 0.001），提示高水平的CD 14可能参与了冠心病的发病机制。通过进行鸟枪蛋白质组学，我们进一步揭示了CD 14相关的炎症反应网络可能在CAD中发挥重要作用。总之，目前的研究表明，在CAD患者中，尿液中CD 14的释放加上更多的CD 14+单核细胞与CAD的严重程度显著相关，指出尿液CD 14作为一种新的非侵入性生物标志物的潜在应用，用于大规模诊断筛选易感CAD患者。
Inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Recently, urinary proteins were found to be useful markers for reflecting inflammation status of different organs. To identify potential biomarker for diagnosis of CAD, we performed one-dimensional SDS-gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Among the proteins differentially expressed in urine samples, monocyte antigen CD14 was found to be consistently expressed in higher amounts in the CAD patients as compared to normal controls. Using enzyme-linked immunosorbent assays to analyze the concentrations of CD14 in urine and serum, we confirmed that urinary CD14 levels were significantly higher in patients (n = 73) with multi-vessel and single vessel CAD than in normal control (n = 35) (P < 0.001). Logistic regression analysis further showed that urinary CD14 concentration level is associated with severity or number of diseased vessels and SYNTAX score after adjustment for potential confounders. Concomitantly, the proportion of CD14+ monocytes was significantly increased in CAD patients (59.7 ± 3.6%) as compared with healthy controls (14.9 ± 2.1%) (P < 0.001), implicating that a high level of urinary CD14 may be potentially involved in mechanism(s) leading to CAD pathogenesis. By performing shotgun proteomics, we further revealed that CD14-associated inflammatory response networks may play an essential role in CAD. In conclusion, the current study has demonstrated that release of CD14 in urine coupled with more CD14+ monocytes in CAD patients is significantly correlated with severity of CAD, pointing to the potential application of urinary CD14 as a novel noninvasive biomarker for large-scale diagnostic screening of susceptible CAD patients.
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