Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach

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.

Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

“…Thus, an integrated analysis of UPLC-Q-TOF/MS-based metabolomics and iTRAQ-based proteomics profiling is promising and may help to obtain a comprehensive picture of plasma after DAI, which could provide further important insights into the pathophysiology of DAI. In the preliminary iTRAQ-based proteomics experiment, three individual plasma samples collected from each of the three groups were equivalently pooled to minimize biological variation [7,16]. To the best of our knowledge, this is the first study addressing this issue using an integrated metabolomics and proteomics approach.…”

“…It is generally known that acetone is a product of acetyl-CoA, and can produce ketone bodies be used as a vital source of energy for the brain under special physiological and pathological conditions [17]. The significant up-regulation of acetone may suggest the elevated flux from acetyl-CoA into acetoacetyl-CoA [16]. Combined with the results of remarkable down-regulation of glucose identified in our previous study, significantly increased acetone may imply an impaired tricarboxylic acid (TCA) cycle in mitochondria and reduced ATP synthesis after DAI [17,18].…”

Screening and Identification of Pregnancy Zone Protein and Leucine‐Rich Alpha‐2‐Glycoprotein as Potential Serum Biomarkers for Early‐Onset Myocardial Infarction using Protein Profile Analysis

“…Cheow and co‐workers performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina, acute myocardial infarction, and healthy control subjects. The expression of nine proteins is modulated by twofold in myocardial injuries relative to stable angina, including six upregulated proteins (α‐1‐antichymotrypsin, CRP, serum amyloid A protein, α‐1‐acid glycoprotein 2, carboxypeptidase N subunit 2, and actin, cytoplasmic 2) and three downregulated proteins (Apo A‐IV, Lumican, and α‐ N ‐acetylglucosaminidase) . In addition, Cubedo and co‐workers identified clusterin as an important biomarker of acute new‐onset MI by using 2DE–TOF‐MS …”

Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma

“…Other significantly altered inflammatory response proteins included the acute-phase proteins alpha-1-acid glycoprotein 2 and alpha-1-antichymotrypsin, which were both increased in abundance within lesions from women when compared to men, with specific increased abundances within internal control and plaque centre regions respectively. Alpha-1-acid glycoprotein 2, also known as orosomucoid-2, has been found at increased levels in patients with acute myocardial infarction and has anti-inflammatory properties [27]. Vascular expression of alpha-1-antichymotrypsin has been associated with human vascular disease, both in carotid atherosclerosis and abdominal aortic aneurysm, with local increases seen in atherosclerosis where it has been speculated to aide plaque stability [28].…”