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

Thong Huy Cao (Lead / Corresponding author), Donald J. l. Jones, Adriaan A. Voors, Paulene A. Quinn, Jatinderpal K. Sandhu, Daniel C. S. Chan, Helen Parry, Pradeep Mohan, Ify Mordi, Iziah E. Sama, Stefan D. Anker, John G. F. Cleland, Kenneth Dickstein, Gerasimos S. Filippatos, Hans L. Hillege, Marco Metra, Piotr Ponikowski, Nilesh J. Samani, Dirk Jan van Veldhuisen, Faiez ZannadChim Lang, Leong Loke Ng

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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.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalEuropean Journal of Heart Failure
Volume22
Issue number1
Early online date6 Nov 2019
DOIs
Publication statusPublished - Jan 2020

Keywords

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

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    Cite this

    Cao, T. H., Jones, D. J. L., Voors, A. A., Quinn, P. A., Sandhu, J. K., Chan, D. C. S., Parry, H., Mohan, P., Mordi, I., Sama, I. E., Anker, S. D., Cleland, J. G. F., Dickstein, K., Filippatos, G. S., Hillege, H. L., Metra, M., Ponikowski, P., Samani, N. J., van Veldhuisen, D. J., ... Ng, L. L. (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), 70-80. https://doi.org/10.1002/ejhf.1608