title: A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction.
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 1h, 1day and 10day 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 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.
  
  
  CONCLUSIONS
  The comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI.
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea; Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Nam
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea.
authors.forename: Youngae
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: dhryu@skku.edu.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Ryu
authors.affiliation: Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul 03759, Republic of Korea; Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Republic of Korea. Electronic address: gshwang@kbsi.re.kr.
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008026:Ligation; D008297:Male; D055432:Metabolomics; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
keywords: Integrative omics analysis; Lipidomics; Metabolomics; Myocardial infarction; Transcriptomics