A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction

作者：Nam Miso; Jung Youngae; Ryu Do Hyun; Hwang Geum Sook

来源：International Journal of Cardiology, 2017, 227: 239-246.

DOI：10.1016/j.ijcard.2016.11.127

• Integrative omics analysis
• Myocardial infarction
• Metabolomics
• Lipidomics
• Transcriptomics

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.

• 出版日期2017-1-15