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Eur J Heart Fail. 2019 Nov 6. doi: 10.1002/ejhf.1608. [Epub ahead of print]

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

Author information

1
Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
2
Leicester Cancer Research Centre, Leicester Royal Infirmary, University of Leicester, Leicester, UK.
3
Department of Cardiology, University of Groningen, Groningen, The Netherlands.
4
Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
5
Division of Cardiology and Metabolism; Department of Cardiology (CVK), Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charité Universitätsmedizin Berlin, Berlin, Germany.
6
Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
7
University of Bergen, Stavanger University Hospital, Stavanger, Norway.
8
Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
9
Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
10
Department of Heart Diseases, Wroclaw Medical University and Cardiology Department, Military Hospital, Wroclaw, Poland.
11
Inserm CIC 1433, Université de Lorraine, Nancy, France.

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.

KEYWORDS:

Heart failure; Mass spectrometry; Metabolism; Pathogenesis; Proteomics; Treatment target

PMID:
31692186
DOI:
10.1002/ejhf.1608

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