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European Journal of Heart Failure 2006 8(7):687-693; doi:10.1016/j.ejheart.2006.01.005
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© 2006 European Society of Cardiology

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

Eric E. Morgana, Margaret P. Chandlera, Martin E. Youngb, Tracy A. McElfresha, Theodore A. Kunga, Julie H. Rennisona, Kou-Yi Tserngc, Brian D. Hoitd and William C. Stanleya,*

a Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4970, USA
b Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA
c Veteran Affairs Medical Reseach Center, Cleveland, OH, USA
d Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA

* Corresponding author. Tel.: +1 216 368 5585; fax: +1 216 368 3952. E-mail address: wcs4{at}case.edu (W.C. Stanley).


   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} (PPAR{alpha}) and retinoid X receptor {alpha} (RXR{alpha}). We assessed mRNA and protein expression of PPAR{alpha} and RXR{alpha}, 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 PPAR{alpha} and RXR{alpha} 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.

Key Words: Cardiac • Ceramide • Metabolism • PPAR{alpha} • RXR{alpha}

Received May 20, 2005; Revised September 17, 2005; Accepted January 12, 2006


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