Research Article S-Nitrosylation Proteome Profile of Peripheral Blood Mononuclear Cells in Human Heart Failure Sue-jie Koo, 1 Heidi M. Spratt, 2,3 Kizhake V. Soman, 4 Susan Stafford, 4 Shivali Gupta, 5 John R. Petersen, 1 Maria P. Zago, 6 Muge N. Kuyumcu-Martinez, 4 Allan R. Brasier, 3,7 John E. Wiktorowicz, 3,4,8 and Nisha Jain Garg 1,5,8 1 Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA 2 Department Preventive Medicine and Community Health, UTMB, Galveston, TX 77555, USA 3 Institute for Translational Sciences, UTMB, Galveston, TX 77555, USA 4 Department of Biochemistry and Molecular Biology, Sealy Center of Molecular Medicine, UTMB, Galveston TX 77555, USA 5 Department of Microbiology and Immunology, UTMB, Galveston, TX 77555, USA 6 Instituto de Patolog´ ıa Experimental, CONICET-UNSa, 4400 Salta, Argentina 7 Department of Internal Medicine-Endocrinology, UTMB, Galveston, TX 77555, USA 8 Institute for Human Infections and Immunity, UTMB, Galveston, TX 77555, USA Correspondence should be addressed to John E. Wiktorowicz; jowiktor@utmb.edu and Nisha Jain Garg; nigarg@utmb.edu Received 30 January 2016; Revised 7 April 2016; Accepted 16 May 2016 Academic Editor: Christoph H. Borchers Copyright © 2016 Sue-jie Koo et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Nitric oxide (NO) protects the heart against ischemic injury; however, NO- and superoxide-dependent S-nitrosylation (S-NO) of cysteines can afect function of target proteins and play a role in disease outcome. We employed 2D-GE with thiol-labeling FL- maleimide dye and MALDI-TOF MS/MS to capture the quantitative changes in abundance and S-NO proteome of HF patients (versus healthy controls,  = 30/group). We identifed 93 diferentially abundant (59-increased/34-decreased) and 111 S-NO- modifed (63-increased/48-decreased) protein spots, respectively, in HF subjects (versus controls, fold-change |≥1.5|,  ≤ 0.05). Ingenuity pathway analysis of proteome datasets suggested that the pathways involved in phagocytes’ migration, free radical production, and cell death were activated and fatty acid metabolism was decreased in HF subjects. Multivariate adaptive regression splines modeling of datasets identifed a panel of proteins that will provide >90% prediction success in classifying HF subjects. Proteomic profling identifed ATP-synthase, thrombospondin-1 (THBS1), and vinculin (VCL) as top diferentially abundant and S- NO-modifed proteins, and these proteins were verifed by Western blotting and ELISA in diferent set of HF subjects. We conclude that diferential abundance and S-NO modifcation of proteins serve as a mechanism in regulating cell viability and free radical production, and THBS1 and VCL evaluation will potentially be useful in the prediction of heart failure. 1. Introduction Of the 57 million global deaths annually, 17.3 million (∼30%) are due to cardiovascular diseases [1, 2]. Heart failure (HF) is a clinical syndrome that manifests as a consequence of the diverse factors including myocardial infarction, hyperten- sion, cardiomyopathies, and atrial fbrillation. Te intimate relationship of the micro- and macroenvironment with the cardiomyocytes results in cellular events that may be impor- tant to the initiation and propagation of HF, though a clear understanding of the molecular mechanisms underlying HF is not available. Some studies have identifed HF-associated alterations in Ca 2+ handling, energy metabolism, and con- tractile function in experimental models (reviewed in [3]); however, how these processes promote HF pathophysiology and if these processes are relevant to human HF remain unclear. Nitric oxide (NO) protects the heart against ischemic injury, and NO-based therapy is part of the standard of care in patients with heart failure [4]. Te classic view holds that Hindawi Publishing Corporation International Journal of Proteomics Volume 2016, Article ID 1384523, 19 pages http://dx.doi.org/10.1155/2016/1384523