Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury
Gregory D. Lewis, … , Marc S. Sabatine, Robert E. Gerszten
Gregory D. Lewis, … , Marc S. Sabatine, Robert E. Gerszten
Published October 1, 2008; First published September 2, 2008
Citation Information: J Clin Invest. 2008;118(10):3503-3512. https://doi.org/10.1172/JCI35111.
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Technical Advance Cardiology

Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury

Abstract

Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry–based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states.

Authors

Gregory D. Lewis, Ru Wei, Emerson Liu, Elaine Yang, Xu Shi, Maryann Martinovic, Laurie Farrell, Aarti Asnani, Marcoli Cyrille, Arvind Ramanathan, Oded Shaham, Gabriel Berriz, Patricia A. Lowry, Igor F. Palacios, Murat Taşan, Frederick P. Roth, Jiangyong Min, Christian Baumgartner, Hasmik Keshishian, Terri Addona, Vamsi K. Mootha, Anthony Rosenzweig, Steven A. Carr, Michael A. Fifer, Marc S. Sabatine, Robert E. Gerszten

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Figure 3

Metabolites whose levels significantly changed from baseline at 60, 120, and 240 minutes in PMI patients assessed in an independent SMI cohort.

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Metabolites whose levels significantly changed from baseline at 60, 120,...
(A) Black bars denote average of median changes across the 3 time points compared with baseline values in PMI patients. White bars denote relative levels of each metabolite in patients presenting with SMI compared with control patients presenting to the cardiac catheterization suite with nonacute cardiovascular disease. (B) Composite scores for metabolites in A, derived by taking the weighted sum of metabolites that increased in PMI minus the sum of metabolites that decreased in PMI. Boxes denote interquartile range, lines denote median, and whiskers denote tenth and ninetieth percentiles. (C) Receiver-operating-characteristic curve for composite metabolite scores for each patient in the SMI cohort (cases) and the second control cohort (controls). AUC (mean ± SEM) is shown.