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

被引：226

作者：

Lewis, Gregory D. ^{[1
,2
,3
,4
]}

Wei, Ru ^{[4
]}

Liu, Emerson ^{[1
,2
,3
]}

Yang, Elaine ^{[4
]}

Shi, Xu ^{[2
]}

Martinovic, Maryann ^{[1
]}

Farrell, Laurie ^{[1
]}

Asnani, Aarti ^{[1
,2
,4
]}

Cyrille, Marcoli ^{[2
]}

Ramanathan, Arvind ^{[4
]}

Shaham, Oded ^{[4
,5
]}

Berriz, Gabriel ^{[6
]}

Lowry, Patricia A. ^{[1
]}

Palacios, Igor F. ^{[1
]}

Tasan, Murat ^{[6
]}

Roth, Frederick P. ^{[6
]}

Min, Jiangyong ^{[7
]}

Baumgartner, Christian ^{[8
]}

Keshishian, Hasmik ^{[4
]}

Addona, Terri ^{[4
]}

Mootha, Vamsi K. ^{[4
,5
]}

Rosenzweig, Anthony ^{[7
]}

Carr, Steven A. ^{[4
]}

Fifer, Michael A. ^{[1
]}

Sabatine, Marc S. ^{[1
,3
,9
]}

Gerszten, Robert E. ^{[1
,2
,3
,4
]}

机构：

[1] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA

[4] MIT & Harvard, Broad Inst, Cambridge, MA USA

[5] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[6] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[7] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA

[8] Univ Hlth Sci Med Informat & Technol UMIT, Res Grp Clin Bioinformat, Tyrol, Austria

[9] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 10期

关键词：

D O I：

10.1172/JCI35111

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：3503 / 3512

页数：10

共 48 条

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