Metabolomic identification of novel biomarkers of myocardial ischemia

Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardi...

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Published in:Circulation (New York, N.Y.) N.Y.), 2005-12, Vol.112 (25), p.3868-3875
Main Authors: SABATINE, Marc S, LIU, Emerson, MORROW, David A, HELLER, Eric, MCCARROLL, Robert, WIEGAND, Roger, BERRIZ, Gabriel F, ROTH, Frederick P, GERSZTEN, Robert E
Format: Article
Language:English
Subjects:
Adenosine Monophosphate - metabolism
Aged
Biological and medical sciences
Biomarkers - blood
Biomarkers - metabolism
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiovascular system
Case-Control Studies
Chromatography, High Pressure Liquid
Citric Acid - metabolism
Coronary heart disease
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Exercise Test
Female
Heart
Humans
Lactic Acid - blood
Male
Medical sciences
Metabolism - physiology
Middle Aged
Muscle, Skeletal - metabolism
Myocardial Ischemia - diagnosis
Pharmacology. Drug treatments
Risk
Spectrometry, Mass, Electrospray Ionization
Vasodilator agents. Cerebral vasodilators
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Summary:Recognition of myocardial ischemia is critical both for the diagnosis of coronary artery disease and the selection and evaluation of therapy. Recent advances in proteomic and metabolic profiling technologies may offer the possibility of identifying novel biomarkers and pathways activated in myocardial ischemia. Blood samples were obtained before and after exercise stress testing from 36 patients, 18 of whom demonstrated inducible ischemia (cases) and 18 of whom did not (controls). Plasma was fractionated by liquid chromatography, and profiling of analytes was performed with a high-sensitivity electrospray triple-quadrupole mass spectrometer under selected reaction monitoring conditions. Lactic acid and metabolites involved in skeletal muscle AMP catabolism increased after exercise in both cases and controls. In contrast, there was significant discordant regulation of multiple metabolites that either increased or decreased in cases but remained unchanged in controls. Functional pathway trend analysis with the use of novel software revealed that 6 members of the citric acid pathway were among the 23 most changed metabolites in cases (adjusted P=0.04). Furthermore, changes in 6 metabolites, including citric acid, differentiated cases from controls with a high degree of accuracy (P
ISSN:0009-7322
1524-4539
DOI:10.1161/circulationaha.105.569137