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Title: Myocardial injury is distinguished from stable angina by a set of candidate plasma biomarkers identified using iTRAQ/MRM-based approach
Authors: Cheow, Esther Sok Hwee
Cheng, Woo Chin
Yap, Terence
Dutta, Bamaprasad
Lee, Chuen Neng
Kleijn, Dominique P. V. de
Sorokin, Vitaly
Sze, Siu Kwan
Keywords: Atherosclerosis
DRNTU::Science::Biological sciences
Cardiovascular Disease
Issue Date: 2017
Source: Cheow, E. S. H., Cheng, W. C., Yap, T., Dutta, B., Lee, C. N., Kleijn, D. P. V. d., . . . Sze, S. K. (2017). Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach. Journal of Proteome Research, 17(1), 499-515. doi:10.1021/acs.jproteome.7b00651
Series/Report no.: Journal of Proteome Research
Abstract: The lack of precise biomarkers that identify patients at risk for myocardial injury and stable angina delays administration of optimal therapy. Hence, the search for noninvasive biomarkers that could accurately stratify patients with impending heart attack, from patients with stable coronary artery disease (CAD), is urgently needed in the clinic. Herein, we performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina (NMI), acute myocardial infarction (MI), and healthy control subjects (Ctrl). We detected a total of 371 proteins with high confidence (FDR < 1%, p < 0.05) including 53 preliminary biomarkers that displayed ≥2-fold modulated expression in patients with CAD (27 associated with atherosclerotic stable angina, 26 with myocardial injury). In the verification phase, we used label-free LC–MRM-MS-based targeted method to verify the preliminary biomarkers in pooled plasma, excluded peptides that were poorly distinguished from background, and performed further validation of the remaining candidates in 49 individual plasma samples. Using this approach, we identified a final panel of eight novel candidate biomarkers that were significantly modulated in CAD (p < 0.05) including proteins associated with atherosclerotic stable angina that were implicated in endothelial dysfunction (F10 and MST1), proteins associated with myocardial injury reportedly involved in plaque destabilization (SERPINA3, CPN2, LUM), and in tissue protection/repair mechanisms (ORM2, ACTG1, NAGLU). Taken together, our data showed that candidate biomarkers with potential diagnostic values can be successfully detected in nondepleted human plasma using an iTRAQ/MRM-based discovery-validation approach and demonstrated the plausible clinical utility of the proposed panel in discriminating atherosclerotic stable angina from myocardial injury in the studied cohort.
ISSN: 1535-3893
DOI: 10.1021/acs.jproteome.7b00651
Rights: © 2017 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: open
Fulltext Availability: With Fulltext
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