A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction. (15th January 2017)

• Record Type: Journal Article
• Authors: Nam, Miso; Jung, Youngae; Ryu, Do Hyun; Hwang, Geum-Sook
• Is Part Of: International journal of cardiology. Volume 227(2017)
• Page Start: 239
• Page End: 246
• Publication Date: 2017-01-15
• Subjects: Integrative omics analysis -- Myocardial infarction -- Metabolomics -- Lipidomics -- Transcriptomics; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2016.11.127
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: 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 S-adenosylmethionine (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 methyltransferases, were decreased in the MI 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 β-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.