title: Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients.
abstract: Coronary artery disease (CAD) is a major cause of mortality and morbidity. Noninvasive proteome analysis could guide clinical evaluation and early/preventive treatment. Under routine clinical conditions, urine of 67 patients presenting with symptoms suspicious for CAD were analyzed by capillary electrophoresis directly coupled with mass spectrometry (CE-MS). All patients were subjected to coronary angiography and either assigned to a CAD or non-CAD group. A training set of 29 patients was used to establish CAD and non-CAD-associated proteome patterns of plasma as well as urine. Significant discriminatory power was achieved in urine but not in plasma. Therefore, urine proteomic analysis of further 38 patients was performed in a blinded study. A combination of 17 urinary polypeptides allowed separation of both groups in the test set with a sensitivity of 81%, a specificity of 92%, and an accuracy of 84%. Sequencing of urinary marker peptides identified fragments of collagen alpha1 (I and III), which we furthermore demonstrated to be expressed in atherosclerotic plaques of human aorta. In conclusion, specific CE-MS polypeptide patterns in urine were associated with significant CAD in patients with angina-typical symptoms. These promising findings need to be further evaluated in regard to reliability of a urine-based screening method with the potential of improving the diagnostic approaches for CAD.
authors.affiliation: Department of Cardiology and Angiology, University Hospital, Freiburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: von Zur Muhlen
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.forename: Petra
authors.initials: P
authors.lastname: Zuerbig
authors.forename: Marcus
authors.initials: M
authors.lastname: Kellmann
authors.forename: Mario
authors.initials: M
authors.lastname: Brasse
authors.forename: Natalie
authors.initials: N
authors.lastname: Meert
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Vanholder
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: Yung Chih
authors.initials: YC
authors.lastname: Chen
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016000:Cluster Analysis; D003094:Collagen / Q000737:chemistry; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*; D019075:Electrophoresis, Capillary / Q000379:methods; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010455:Peptides / Q000737:chemistry / Q000652:urine; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D013696:Temperature; D014556:Urine
chemical_list: D015415:Biomarkers; D010455:Peptides; D020543:Proteome; D003094:Collagen