Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.
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The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.
Gene Expression Profiling
Protein Interaction Mapping
Protein Interaction Maps
Reproducibility of Results
Published Version (Please cite this version)10.1371/journal.pone.0104157
Publication InfoSchechter, Matthew A; Hsieh, Michael KH; Njoroge, Linda W; Thompson, J Will; Soderblom, Erik J; Feger, Bryan J; ... Bowles, Dawn E (2014). Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure. PLoS One, 9(8). pp. e104157. 10.1371/journal.pone.0104157. Retrieved from https://hdl.handle.net/10161/13939.
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Assistant Professor in Surgery
Research Program Leader, Tier 1
A scientist with basic and clinical research training, who is passionate about supporting Duke investigators and strengthening research integrity.
Assistant Professor in Medicine
The Hirschey Lab in the Duke Molecular Physiology Institute, and the Departments of Medicine and Pharmacology & Cancer Biology at Duke University studies different aspects of metabolic control, mitochondrial signaling, and cellular processes regulating human health and disease.
Assistant Professor of Medicine
Professor of Surgery
Associate Professor in Medicine
Assistant Research Professor of Cell Biology
Assistant Research Professor of Pharmacology & Cancer Biology
Dr. Thompson's research focuses on the development and deployment of proteomics and metabolomics mass spectrometry techniques for the analysis of biological systems. He is the Assistant Director of the Proteomics and Metabolomics Shared Resource in the Duke School of Medicine. In this role, he enjoys utilizing mass spectrometry 'omics techniques in research collaborations with investigators throughout the Duke community.
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