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Plasma proteomic approach in patients with heart failure : insights into pathogenesis of disease progression and potential novel treatment targets

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Cao, Thong H., Jones, Donald J. L., Voors, Adriaan A., Quinn, Paulene A., Sandhu, Jatinderpal K., Chan, Daniel C.S., Parry, Helen M., Mohan, Mohapradeep, Mordi, Ify R., Sama, Iziah E. et al.
(2020) Plasma proteomic approach in patients with heart failure : insights into pathogenesis of disease progression and potential novel treatment targets. European Journal of Heart Failure, 22 (1). pp. 70-80. doi:10.1002/ejhf.1608

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Official URL: http://dx.doi.org/10.1002/ejhf.1608

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Abstract

Aims
To provide insights into pathogenesis of disease progression and potential novel treatment targets for patients with heart failure by investigation of the plasma proteome using network analysis.

Methods and results
The plasma proteome of 50 patients with heart failure who died or were rehospitalised were compared with 50 patients with heart failure, matched for age and sex, who did not have an event. Peptides were analysed on two‐dimensional liquid chromatography coupled to tandem mass spectrometry (2D LC ESI‐MS/MS) in high definition mode (HDMSE). We identified and quantified 3001 proteins, of which 51 were significantly up‐regulated and 46 down‐regulated with more than two‐fold expression changes in those who experienced death or rehospitalisation. Gene ontology enrichment analysis and protein–protein interaction networks of significant differentially expressed proteins discovered the central role of metabolic processes in clinical outcomes of patients with heart failure. The findings revealed that a cluster of proteins related to glutathione metabolism, arginine and proline metabolism, and pyruvate metabolism in the pathogenesis of poor outcome in patients with heart failure who died or were rehospitalised.

Conclusions
Our findings show that in patients with heart failure who died or were rehospitalised, the glutathione, arginine and proline, and pyruvate pathways were activated. These pathways might be potential targets for therapies to improve poor outcomes in patients with heart failure.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School > Health Sciences > Mental Health and Wellbeing
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Heart failure , Heart -- Diseases , Heart -- Diseases -- Treatment , Plasma spectroscopy , Proteomics
Journal or Publication Title: European Journal of Heart Failure
Publisher: John Wiley & Sons Ltd.
ISSN: 1388-9842
Official Date: January 2020
Dates:
DateEvent
January 2020Published
6 November 2019Available
19 August 2019Accepted
Volume: 22
Number: 1
Page Range: pp. 70-80
DOI: 10.1002/ejhf.1608
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
FP7-242209-BIOSTAT-CHFSeventh Framework Programmehttp://dx.doi.org/10.13039/100011102
EudraCT 2010-020808-29Seventh Framework Programmehttp://dx.doi.org/10.13039/100011102
John and Lucille van Geest FoundationNottingham Trent Universityhttp://dx.doi.org/10.13039/100010016
FS/15/10/3122British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
UNSPECIFIED[NIHR] National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272

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