Abstract
Timely and accurate confirmation of the occurrence of silent myocardial ischemia (SMI) is critical both for prevention and therapy management. Metabolomics assay may offer an alternative for SMI differentiation and altered biomolecule discovery in addition to traditional measures. In this study, plasma samples were obtained from 14 diagnosed SMI subjects and 25 healthy controls and analyzed by liquid chromatography coupled with quadrupole‐time‐of‐flight mass spectrometry in view of metabolomics. Obtained data were subjected to orthogonal signal correction partialleast‐squares discriminate analysis. Multi‐variate statistic analysis indicated a clear separation between the two studied groups. Plasma concentration fluctuation of four kinds of phospholipids showed tight relationship with the occurrence of SMI, among which 1‐linoleoylglycerophosphocholine (C18:2) was decreased statistically in SMI population (P=0.01). The plasma phospholipids' changes were before enzymatic alteration in SMI, which might be a useful complementary reference to facilitate SMI diagnosis. J. Clin. Lab. Anal. 23:45–50, 2009. © 2009 Wiley‐Liss, Inc.
Keywords: myocardial ischemia, metabolomics, phospholipids
REFERENCES
- 1. Cohn PF, Fox KM, Daly C. Silent myocardial ischemia. Circulation 2003;108:1263–1277. [DOI] [PubMed] [Google Scholar]
- 2. Beishuizen ED, Jukema JW, Tamsma JT, et al. No effect of statin therapy on silent myocardial ischemia in patients with type 2 diabetes without manifest cardiovascular disease. Diabetes Care 2005;28:1675–1679. [DOI] [PubMed] [Google Scholar]
- 3. Cohn PF. Should silent ischemia be treated in asymptomatic individuals? Circulation 1990;82:II149–II154. [PubMed] [Google Scholar]
- 4. Erikssen J. Prognostic importance of silent ischemia during long‐term follow‐up of patients with coronary artery disease. A short review based on own experience and current literature. Herz 1987;12:359–368. [PubMed] [Google Scholar]
- 5. Weiner DA, Ryan TJ, McCabe CH, et al. Significance of silent myocardial ischemia during exercise testing in patients with coronary artery disease. Am J Cardiol 1987;59:725–729. [DOI] [PubMed] [Google Scholar]
- 6. Mahmarian JJ, Boyce TM, Goldberg RK, Cocanougher MK, Roberts R, Verani MS. Quantitative exercise thallium‐201 single photon emission computed tomography for the enhanced diagnosis of ischemic heart disease. J Am Coll Cardiol 1990;15:318–329. [DOI] [PubMed] [Google Scholar]
- 7. He ZX, Hedrick TD, Pratt CM, et al. Severity of coronary artery calcification by electron beam computed tomography predicts silent myocardial ischemia. Circulation 2000;101:244–251. [DOI] [PubMed] [Google Scholar]
- 8. Lindon JC, Holmes E, Nicholson JK. Metabonomics: systems biology in pharmaceutical research and development. Curr Opin Mol Ther 2004;6:265–272. [PubMed] [Google Scholar]
- 9. Clarke CJ, Haselden JN. Metabolic profiling as a tool for understanding mechanisms of toxicity. Toxicol Pathol 2008;36:140–147. [DOI] [PubMed] [Google Scholar]
- 10. Robert MM, Benoit JB, Lopez‐Martinez G, Elnitsky MA, Lee RE Jr, Denlinger DL. Metabolomics reveals unique and shared metabolic changes in response to heat shock, freezing and desiccation in the Antarctic midge, Belgica antarctica . J Insect Physiol 2008. [DOI] [PubMed] [Google Scholar]
- 11. Shyur LF, Yang NS. Metabolomics for phytomedicine research and drug development. Curr Opin Chem Biol 2008;12:66–71. [DOI] [PubMed] [Google Scholar]
- 12. Brindle JT, Antti H, Holmes E, et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H‐NMR‐based metabonomics. Nat Med 2002;8:1439–1444. [DOI] [PubMed] [Google Scholar]
- 13. Sabatine MS, Liu E, Morrow DA, et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation 2005;112:3868–3875. [DOI] [PubMed] [Google Scholar]
- 14. Ferreira JF, Cesar LA, Gruppi CJ, et al. Silent myocardial ischemia in patients with stable coronary artery disease receiving conventional antianginal drug therapy. Arq Bras Cardiol 2007;89:283–288. [DOI] [PubMed] [Google Scholar]
- 15. Robert MM, Benoit JB, Lopez‐Martinez G, Elnitsky MA, Lee RE Jr, Denlinger DL. Metabolomics reveals unique and shared metabolic changes in response to heat shock, freezing and desiccation in the Antarctic midge, Belgica antarctica . J Insect Physiol 2008. [DOI] [PubMed] [Google Scholar]
- 16. Shyur LF, Yang NS. Metabolomics for phytomedicine research and drug development. Curr Opin Chem Biol 2008;12:66–71. [DOI] [PubMed] [Google Scholar]
- 17. Lindahl B, Venge P, Wallentin L. Early diagnosis and exclusion of acute myocardial infarction using biochemical monitoring. The BIOMACS Study Group. Biochemicals Markers of Acute Coronary Syndromes. Coron Artery Dis 1995;6:321–328. [DOI] [PubMed] [Google Scholar]
- 18. Lindon JC, Nicholson JK, Holmes E, editors. The Handbook of Metabonomics and Metabolomics. Amsterdam: Elsevier BV, 2007. [Google Scholar]
- 19. Kume N, Cybulsky MI, Gimbrone MA Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 1992;90:1138–1144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Kume N, Gimbrone MA Jr. Lysophosphatidylcholine transcriptionally induces growth factor gene expression in cultured human endothelial cells. J Clin Invest 1994;93:907–911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Jing Q, Xin SM, Zhang WB, Wang P, Qin YW, Pei G. Lysophosphatidylcholine activates p38 and p42/44 mitogen‐activated protein kinases in monocytic THP‐1 cells, but only p38 activation is involved in its stimulated chemotaxis. Circ Res 2000;87:52–59. [DOI] [PubMed] [Google Scholar]
- 22. Koh JS, Wang Z, Levine JS. Cytokine dysregulation induced by apoptotic cells is a shared characteristic of murine lupus. J Immunol 2000;165:4190–4201. [DOI] [PubMed] [Google Scholar]
- 23. Choy PC, Chan M, Hatch G, Man RY. Phosphatidylcholine metabolism in ischemic and hypoxic hearts. Mol Cell Biochem 1992;116:53–58. [DOI] [PubMed] [Google Scholar]
- 24. Bai Y, Wang J, Lu Y, Shan H, Yang B, Wang Z. Phospholipid lysophosphatidylcholine as a metabolic trigger and HERG as an ionic pathway for extracellular K accumulation and “short QT syndrome” in acute myocardial ischemia. Cell Physiol Biochem 2007;20:417–428. [DOI] [PubMed] [Google Scholar]