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Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism.

AbstractOBJECTIVES:
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)].
CONCLUSION:
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.
AuthorsN Rosenblatt-Velin, C Montessuit, I Papageorgiou, J Terrand, R Lerch
JournalCardiovascular research (Cardiovasc Res) Vol. 52 Issue 3 Pg. 407-16 (Dec 2001) ISSN: 0008-6363 [Print] Netherlands
PMID11738057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Fatty Acids
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Slc2a1 protein, rat
  • Slc2a4 protein, rat
  • Acyl-CoA Dehydrogenases
Topics
  • Acyl-CoA Dehydrogenases (metabolism)
  • Animals
  • Biomarkers (analysis)
  • Blotting, Northern (methods)
  • Blotting, Western (methods)
  • Energy Metabolism
  • Fatty Acids (genetics, metabolism)
  • Gene Expression Regulation
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Heart Failure (diagnosis, metabolism)
  • Models, Animal
  • Monosaccharide Transport Proteins (metabolism)
  • Muscle Proteins
  • Myocardial Infarction (metabolism)
  • Rats
  • Rats, Inbred Strains
  • Time Factors
  • Ventricular Remodeling

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