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J Clin Invest DOI:10.1172/JCI35111

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

Publication TypeJournal Article
Year of Publication2008
AuthorsLewis, GD, Wei, R, Liu, E, Yang, E, Shi, X, Martinovic, M, Farrell, L, Asnani, A, Cyrille, M, Ramanathan, A, Shaham, O, Berriz, G, Lowry, PA, Palacios, IF, Taşan, M, Roth, FP, Min, J, Baumgartner, C, Keshishian, H, Addona, T, Mootha, VK, Rosenzweig, A, Carr, SA, Fifer, MA, Sabatine, MS, Gerszten, RE
JournalJ Clin Invest
Date Published2008 Oct
KeywordsAged, Animals, Biomarkers, Cells, Cultured, Coronary Sinus, Female, Heart Injuries, Humans, Isotopes, Kinetics, Male, Middle Aged, Myocardial Infarction, Myocytes, Cardiac, Rats, Reference Standards, Reproducibility of Results, Time Factors

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.


Alternate JournalJ. Clin. Invest.
PubMed ID18769631
PubMed Central IDPMC2525696
Grant ListR01 HL072872 / HL / NHLBI NIH HHS / United States
R01DK081572 / DK / NIDDK NIH HHS / United States
R01 HL083141 / HL / NHLBI NIH HHS / United States
NS054052 / NS / NINDS NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
P50 HG004233 / HG / NHGRI NIH HHS / United States
U01HL083141 / HL / NHLBI NIH HHS / United States
HG003224 / HG / NHGRI NIH HHS / United States
HG0017115 / HG / NHGRI NIH HHS / United States
R01 NS054052 / NS / NINDS NIH HHS / United States
HG004233 / HG / NHGRI NIH HHS / United States
R01 HG003224 / HG / NHGRI NIH HHS / United States
R01 AG017115 / AG / NIA NIH HHS / United States