Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

Abstract

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0104157

Publication Info

Schechter, Matthew A, Michael KH Hsieh, Linda W Njoroge, J Will Thompson, Erik J Soderblom, Bryan J Feger, Constantine D Troupes, Kathleen A Hershberger, et al. (2014). Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure. PLoS One, 9(8). p. e104157. 10.1371/journal.pone.0104157 Retrieved from https://hdl.handle.net/10161/13939.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Thompson

J. Will Thompson

Adjunct Assistant Professor in the Department 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 served as the Assistant Director of the Proteomics and Metabolomics Shared Resource in the Duke School of Medicine from 2007-2021. He currently maintains collaborations in metabolomics and proteomics research at Duke, and develops new tools for chemical analysis as a Principal Scientist at 908 Devices in Carrboro, NC.

Soderblom

Erik James Soderblom

Associate Research Professor of Cell Biology

Director, Proteomics and Metabolomics Core Facility

Feger

Bryan Feger

Medical Writer, Sr

A scientist with basic and clinical research training, who is passionate about supporting Duke investigators and strengthening research integrity. 

Ilkayeva

Olga Ilkayeva

Assistant Professor in Medicine

Olga Ilkayeva, Ph.D., is the Director of the Metabolomics Core Laboratory at Duke Molecular Physiology Institute. She received her Ph.D. training in Cell Regulation from UT Southwestern Medical Center at Dallas, TX. Her postdoctoral research in the laboratory of Dr. Chris Newgard at Duke University Medical Center focused on lipid metabolism and regulation of insulin secretion. As a research scientist at the Stedman Nutrition and Metabolism Center, Dr. Ilkayeva expanded her studies to include the development of targeted mass spectrometry analyses. Currently, she works on developing and validating quantitative mass spectrometry methods used for metabolic profiling of various biological models with emphasis on diabetes, obesity, cardiovascular disease, and the role of gut microbiome in both health and disease.

Hirschey

Matthew Hirschey

Associate Professor of 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.

Foster

Matthew Wolf Foster

Associate Professor in Medicine
Milano

Carmelo Alessio Milano

Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
Moseley

Martin Arthur Moseley

Adjunct Professor in the Department of Cell Biology
Bowles

Dawn Elizabeth Bowles

Assistant Professor in Surgery

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.