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

Abstract

BackgroundMyocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. MethodsWe evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. ResultsA 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 10days 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. ConclusionsThe comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI.