Urinary peptides in heart failure: a link to molecular pathophysiology

He, T. et al. (2021) Urinary peptides in heart failure: a link to molecular pathophysiology. European Journal of Heart Failure, (doi: 10.1002/ejhf.2195) (PMID:33881206) (Early Online Publication)

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Abstract

Aims: Heart failure (HF) is a major public health concern worldwide. The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid‐range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology. Methods and Results: Analysable data from 5,608 participants were available in the Human Urinary Proteome database. The urinary peptide profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and controls matched for sex, age, estimated glomerular filtration rate, systolic and diastolic blood pressure, diabetes and hypertension were compared applying the Mann Whitney test, followed by correction for multiple testing. Unsupervised learning algorithms were applied to investigate groups of similar urinary profiles. 577 urinary peptides significantly associated with HF were sequenced, 447 of which (77%) were collagen fragments. In silico analysis suggested that urinary biomarker abnormalities in HF principally reflect changes in collagen turnover and immune response, both associated with fibrosis. Unsupervised clustering separated study participants into two clusters, with 83% of non‐HF controls allocated to cluster 1, while 65% of patients with HF were allocated to cluster 2 (p<0.0001). No separation based on HF subtype was detectable. Conclusions: HF, irrespective of ejection fraction subtype, was associated with differences in abundance of urinary peptides reflecting collagen turnover and inflammation. These peptides should be studied as tools in early detection, prognostication, and prediction of therapeutic response.

Item Type:Articles
Additional Information:AC, CD, JD, AG, AM, JR, NG, PR, FZ, HM, ZZ, JS, AL are supported by the EU Commission via the HOMAGE (HEALTH-FP7–305507 HOMAGE) project. CD, FZ, HM, JD and JS were previously supported by the EU-MASCARA (HEALTH-FP7–278249) project, and CD and JM receive support from the British Heart Foundation (RE/18/6/34217). TH is supported by the EU Commission via the CaReSyAn Project (MSCA-ITN-2017-Project ID: 764474). VJ is supported by the Deutsche Forschungsgemeinschaft’ (DFG, German Research Foundation) by the Transregional Collaborative Research Centre (TRR 219; Project-ID 322900939) (subproject S-03). PR, NG, FZ are supported by the RHU Fight-HF, a public grant overseen by the French National Research Agency (ANR) as part of the second ‘Investissements d’Avenir’ program (reference: ANR-15-RHUS-0004), and by the French PIA project ‘Lorraine Université d’Excellence’(reference: ANR-15-IDEX-04-LUE). The Stanislas Cohort is sponsored by Nancy CHRU (France); its biobanking is managed by Biological Resource Center Lorrain BB-0033-00035. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. The non-profit Research Institute Alliance for the Promotion of Preventive Medicine received a non-binding grant from OMRON Healthcare Co., Inc., Kyoto, Japan.
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Delles, Professor Christian and Mullen, Dr Bill and Mischak, Professor Harald and Campbell, Dr Ross and Jackson, Dr Colette and McMurray, Professor John and Cannon, Dr Jane
Authors: He, T., Mischak, M., Clark, A. L., Campbell, R. T., Delles, C., Díez, J., Filipatos, G., Mebazaa, A., McMurray, J. J.V., González, A., Raad, J., Stroggilos, R., Bosselmann, H. S., Campbell, A., Kerr, S., Jackson, C. E., Cannon, J. A., Schou, M., Girerd, N., Rossignol, P., McConnachie, A., Rossing, K., Schanstra, J. P., Zannad, F., Vlahou, A., Mullen, W., Jankowski, V., Mischak, H., Zhang, Z., Staessen, J. A., and Latoskinska, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:21 April 2021
Copyright Holders:Copyright © 2021 John Wiley & Sons, Inc.
First Published:First published in European Journal of Heart Failure
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
190458EU-MASCARA - Biomarkers for Cardiovascular DiseaseChristian DellesEuropean Commission (EC)Delles, Dr ChristianInstitute of Cardiovascular & Medical Sciences
190082Generation ScotlandAnna DominiczakOffice of the Chief Scientific Adviser (CSO)CZD/16/6MVLS - College Senior Management