title: Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.
abstract: 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.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Ming-Sheng Hospital, Kaohsiung, Taiwan.
authors: Min-Yi
authors: MY
authors: Lee
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chun-Hao
authors: CH
authors: Huang
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Quantitative Proteomics Center, Center for Research Resources and Development, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chao-Jen
authors: CJ
authors: Kuo
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Chen-Lung Steve
authors: CL
authors: Lin
authors: Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Wen-Ter
authors: WT
authors: Lai
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Quantitative Proteomics Center, Center for Research Resources and Development, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors: Shyh-Horng
authors: SH
authors: Chiou
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000652:urine; D018950:Lipopolysaccharide Receptors / Q000652:urine*; D009000:Monocytes / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D020543:Proteome