title: Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism.
abstract: OBJECTIVE
  Increasing evidence suggests that left ventricular remodeling is associated with a shift from fatty acid to glucose metabolism for energy production. The aim of this study was to determine whether left ventricular remodeling with and without late-onset heart failure after myocardial infarction is associated with regional changes in the expression of regulatory proteins of glucose or fatty acid metabolism.
  
  
  METHODS
  Myocardial infarction was induced in rats by ligation of the left anterior descending coronary artery (LAD). In infarcted and sham-operated hearts the peri-infarction region (5-mm zone surrounding the region at risk), the interventricular septum and the right ventricular free wall were separated for analysis.
  
  
  RESULTS
  At 8 and 20 weeks after LAD ligation, the peri-infarction region and the septum exhibited marked re-expression of atrial natriuretic factor [+252+/-37 and +1093+/-279%, respectively, in the septum (P<0.05)] and of alpha-smooth muscle actin [+34+/-10 and +43+/-14%, respectively, in the septum (P<0.05)]. At 8 weeks, when left ventricular hypertrophy was present without signs of heart failure, myocardial mRNA expression of glucose transporters (GLUT-1 and GLUT-4) was not altered, whereas mRNA expression of medium-chain acyl-CoA dehydrogenase (MCAD) was significantly reduced in the peri-infarction region (-25+/-7%; P<0.05). In hearts exhibiting heart failure 20 weeks after infarct-induction there was a change in all three ventricular regions of both mRNA and protein content of GLUT-1 [+72+/-28 and +121+/-15%, respectively, in the peri-infarction region (P<0.05)] and MCAD [-29+/-9 and -56+/-4%, respectively, in the peri-infarction region (P<0.05)].
  
  
  CONCLUSIONS
  In rats with large myocardial infarction, progression from compensated remodeling to overt heart failure is associated with upregulation of GLUT-1 and downregulation of MCAD in both the peri-infarction region and the septum.
authors.affiliation: Cardiology Center, University Hospital, 24, rue Micheli-du-Crest CH-1211 14, Geneva, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Rosenblatt-Velin
authors.forename: C
authors.initials: C
authors.lastname: Montessuit
authors.forename: I
authors.initials: I
authors.lastname: Papageorgiou
authors.forename: J
authors.initials: J
authors.lastname: Terrand
authors.forename: R
authors.initials: R
authors.lastname: Lerch
mesh_terms: D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D004734:Energy Metabolism; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism*; D023421:Models, Animal; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009203:Myocardial Infarction / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D044944:Acyl-CoA Dehydrogenases