TY - JOUR TI - Plasma proteomic approach in patients with heart failure: insights into pathogenesis of disease progression and potential novel treatment targets AU - Cao, T.H. AU - Jones, D.J.L. AU - Voors, A.A. AU - Quinn, P.A. AU - Sandhu, J.K. AU - Chan, D.C.S. AU - Parry, H.M. AU - Mohan, M. AU - Mordi, I.R. AU - Sama, I.E. AU - Anker, S.D. AU - Cleland, J.G. AU - Dickstein, K. AU - Filippatos, G. AU - Hillege, H.L. AU - Metra, M. AU - Ponikowski, P. AU - Samani, N.J. AU - Van Veldhuisen, D.J. AU - Zannad, F. AU - Lang, C.C. AU - Ng, L.L. JO - European Journal of Heart Failure PY - 2020 VL - 22 TODO - 1 SP - 70-80 PB - John Wiley and Sons Ltd SN - null TODO - 10.1002/ejhf.1608 TODO - arginine; glutathione; plasma protein; proline; pyruvic acid; angiotensin receptor antagonist; dipeptidyl carboxypeptidase inhibitor; proteome, aged; Article; clinical article; controlled study; death; female; gene ontology; glutathione metabolism; heart failure; hospital readmission; human; liquid chromatography-mass spectrometry; male; priority journal; prognosis; protein expression; protein protein interaction; proteomics; disease exacerbation; heart failure; heart left ventricle function; heart stroke volume; percutaneous coronary intervention; plasma; proteomics; tandem mass spectrometry; very elderly, Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Disease Progression; Female; Heart Failure; Humans; Male; Percutaneous Coronary Intervention; Plasma; Proteome; Proteomics; Stroke Volume; Tandem Mass Spectrometry; Ventricular Function, Left TODO - 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. © 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. ER -