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A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction
- A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction
- Nam, Miso; Jung, Youngae; Ryu, Do Hyun; Hwang, Geum-Sook
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- INTERNATIONAL JOURNAL OF CARDIOLOGY
- 0167-5273; 1874-1754
- vol. 227, pp. 239 - 246
- Integrative omics analysis; Myocardial infarction; Metabolomics; Lipidomics; Transcriptomics
- ELSEVIER IRELAND LTD
- SCI; SCIE; SCOPUS
- Background: Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. Methods: We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1 h, 1 day and 10 day after coronary ligation, using global profiling based on metabolomics. Results: A time-dependent increase or decrease in polar and lipid metabolite levels was measured. The Sadenosylmethionine (SAM) concentration and the SAM/S-adenosylhomocysteine (SAH) ratio gradually decreased in a time-dependent manner and were significantly downregulated 10 days after MI. Transcriptome analysis revealed that the levels of coenzyme Q (Coq)-3 and Coq5, both of which are SAM-dependent methyl-transferases, were decreased in theMI groups. These results suggested that dysregulation of SAM may be related to down regulated COQ biosynthetic pathway. In addition, short-chain (C3) and medium-chain (C4-C12) acylcarnitine levels gradually decreased, whereas long-chain acylcarnitine (C14-18) levels increased, owing to a defect in beta-oxidation during ischemia. These changes are related to energy-dependent metabolic pathways, and a subsequent decrease in adenosine triphosphate concentration was observed. Conclusions: The comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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