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

Abstract

OBJECTIVES:

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.

• Authors: N Rosenblatt-Velin, C Montessuit, I Papageorgiou, J Terrand, R Lerch
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 52 Issue 3 Pg. 407-16 (Dec 2001) ISSN: 0008-6363 [Print] England
• PMID: 11738057 (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