|Morgan, E - CASE WESTERN RESERVE|
|Chandler, M - CASE WESTERN RESERVE|
|Mcelfresh, T - CASE WESTERN RESERVE|
|Dung, T - CASE WESTERN RESERVE|
|Renison, J - CASE WESTERN RESERVE|
|Tserng, K - CASE WESTERN RESERVE|
|Hoit, B - CASE WESTERN RESERVE|
|Stanley, W - CASE WESTERN RESERVE|
Submitted to: European Journal of Heart Failure
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 20, 2006
Publication Date: November 20, 2006
Citation: Morgan, E.E., Chandler, M.P., Young, M.E., Mcelfresh, T.A., Dung, T.A., Renison, J.H., Tserng, K.Y., Hoit, B.D., Stanley, W.C. 2006. Dissociation between gene and protein expression of metabolic enzymes in a rodent model of heart failure. European Journal of Heart Failure. 8(7):687-693. Interpretive Summary: Heart disease is the leading cause of death in the United States (U.S.). The number of people with heart failure (a type of heart disease) continues to increase in the U.S.. In order to improve the health of the U.S. population, it is important to understand how diseases, such as heart failure, develop. To find out whether the levels of proteins important for providing energy are changed in the rat heart during heart failure. The results show that the amount of specific proteins in the failing heart does not always match how active the gene is. This work is important, as it suggests that we should investigate proteins in the failing heart, to better understand how this major cause of death in the United States develops.
Technical 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.