Dissociation between gene and protein expression of metabolic enzymes in a rodent model of heart failure

Abstract

Studies in advanced heart failure show down-regulation of fatty acid oxidation genes, possibly due to decreased expression of the nuclear transcription factors peroxisome proliferator activated receptor alpha (PPARalpha) and retinoid X receptor alpha (RXRalpha). We assessed mRNA and protein expression of PPARalpha and RXRalpha, and for several PPAR/RXR regulated metabolic proteins at 8 and 20 weeks following myocardial infarction induced by coronary artery ligation. Infarction resulted in heart failure, as indicated by reduced LV fractional shortening and increased end diastolic area compared to sham. There was a progressive increase in LV end systolic area, myocardial ceramide content and atrial natriuretic peptide mRNA, and a deterioration in LV fractional area of shortening from 8 to 20 weeks. Protein and mRNA expression of PPARalpha and RXRalpha were not different among groups. The mRNA for PPAR/RXR regulated genes (e.g. medium chain acyl-CoA dehydrogenase (MCAD)) was down-regulated at 8 and 20 weeks post-infarction; however, neither the protein expression nor activity of MCAD was reduced compared to sham. In conclusion, reduced mRNA expression of PPAR/RXR regulated genes is not dependent on reduced PPAR/RXR protein expression.