Urinary proteomics pilot study for biomarker discovery and diagnosis in heart failure with reduced ejection fraction

Rossing, K. et al. (2016) Urinary proteomics pilot study for biomarker discovery and diagnosis in heart failure with reduced ejection fraction. PLoS ONE, 11(6), e0157167. (doi: 10.1371/journal.pone.0157167) (PMID:27308822) (PMCID:PMC4911082)

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Background Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Methods and Results Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12.6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin. Conclusion CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure.

Item Type:Articles
Additional Information:The funding organization (European Union; grants EU-MASCARA [HEALTH-2011.2.4.2-2] and HOMAGE [HEALTH-F7- 305507 HOMAGE] as well as the Muremester Laurits P Christensens Fund
Glasgow Author(s) Enlighten ID:Mischak, Professor Harald
Authors: Rossing, K., Bosselmann, H. S., Gustafsson, F., Zhang, Z.-Y., Gu, Y.-M., Kuznetsova, T., Nkuipou-Kenfack, E., Mischak, H., Staessen, J. A., Koeck, T., and Schou, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Published Online:16 June 2016
Copyright Holders:Copyright © 2016 Rossing et al.
First Published:First published in PLoS ONE 11(6);e0157167
Publisher Policy:Reproduced under a Creative Commons License

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