Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease

• Published in: PloS one Vol. 10; no. 2; p. e0117169
• Main Authors: Lee, Min-Yi, Huang, Chun-Hao, Kuo, Chao-Jen, Lin, Chen-Lung Steve, Lai, Wen-Ter, Chiou, Shyh-Horng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-02-2015; Public Library of Science (PLoS)
• Subjects: Acute coronary syndromes; Aged; Antigens; Arteriosclerosis; Atherosclerosis; Biological markers; Biomarkers; Biomarkers - urine; Blood vessels; Body fluids; Cardiology; Cardiovascular disease; Care and treatment; Case-Control Studies; CD14 antigen; Cholesterol; Chromatography; Complications and side effects; Coronary artery; Coronary artery disease; Coronary Artery Disease - diagnosis; Coronary Artery Disease - metabolism; Coronary Artery Disease - urine; Coronary heart disease; Coronary vessels; Diagnosis; Diagnostic systems; Electrophoresis; Gel electrophoresis; Heart diseases; Hospitals; Humans; Immunoassays; Inflammation; Inflammation - metabolism; Inflammation - urine; Inflammatory response; Internal medicine; Lipopolysaccharide Receptors - urine; Lipoproteins; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medical diagnosis; Medicine; Monocytes; Monocytes - metabolism; Organs; Pathogenesis; Patients; Protein expression; Proteins; Proteome - metabolism; Proteomics; Proteomics - methods; Regression analysis; Risk factors; Tandem Mass Spectrometry - methods; Urine; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117169

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.