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

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.

Heart failure in the last year: progress and perspective

“…A recent study demonstrated that glutathione, arginine and proline, and pyruvate pathways were activated in HF patients who died or were rehospitalized. 249 The ubiquitous lysosomal protease cathepsin D is secreted as a response to oxidative stress, but its role in HF was unknown. It has been recently discovered that elevated levels of cathepsin D are associated with HF severity and poor outcome.…”

“…Proteomic processes also represent a field of interest and could be targets for the future. A recent study demonstrated that glutathione, arginine and proline, and pyruvate pathways were activated in HF patients who died or were rehospitalized 249 . The ubiquitous lysosomal protease cathepsin D is secreted as a response to oxidative stress, but its role in HF was unknown.…”

Big Data Approaches in Heart Failure Research

“…The plasma proteome of HF patients has been analyzed extensively to identify biomarkers for HF and their genetic risk-association as well as to understand organ crosstalk via blood stream [ 99 – 101 ]. Egerstedt et al studied the plasma proteome of HF patients in different clinical stages (early HF development, manifest advanced HF, and reversal of HF after heart transplantation) [ 102 ••].…”

Finding a Needle in a Haystack

“…Several studies have examined MS/MS proteomics to evaluate the disease state of HF ( 9 , 44 , 45 , 46 , 47 ). In a study of ischemic cardiomyopathy (ICM), Yi et al.…”

“…The assessment of proteins expressed in a specific state and how these proteins might change over time and with alterations in disease circumstance are notable. Such “proteomics” may reveal previously unrecognized pathophysiological pathways in HF and solidify understanding of the inter-relatedness of known processes ( 9 ). Proteomics allows for testing of thousands of proteins simultaneously, using as little as 1 μl of a sample ( 10 ), which permits rapid and high-throughput discovery of potential biomarkers of HF or identifies druggable targets, thus rapidly translating findings from bench to bedside.…”