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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Abstract
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 |
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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 |
Status: | Published |
Refereed: | Yes |
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: | 1932-6203 |
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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