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European Journal of Heart Failure 2006 8(3):290-294; doi:10.1016/j.ejheart.2005.09.003
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© 2005 European Society of Cardiology

Cardiac PPAR{alpha} expression in patients with dilated cardiomyopathy

Michael Schuppa, Ulrich Kintschera, Jens Fielitzb,d, Jennifer Thomasd, Reinhard Preglac, Roland Hetzerc, Thomas Ungera and Vera Regitz-Zagrosekc,d,*

a Center for Cardiovascular Research (CCR), Institute of Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin CCM, Hessischestr. 3-4, 10115 Berlin, Germany
b Department of Molecular Biology, University of Texas Southwestern Medical Center Dallas, TX 75390-9148, United States
c German Heart Institute, Department of Cardiothoracic and Vascular Surgery Augustenburger Platz 1, 13353 Berlin, Germany
d Center for Cardiovascular Research (CCR), Cardiovascular Disease in Women, Charité-Universitätsmedizin Berlin, CCM Hessischestr. 3-4, 10115 Berlin, Germany

* Corresponding author. Center for Cardiovascular Research (CCR), Cardiovascular Disease in Women, Charité-Universitätsmedizin Berlin CCM, Hessischestr. 3-4, 10115 Berlin, Germany. Tel.: +49 30 450 525172; fax: +49 30 450 525972. E-mail address: vera.regitz-zagrosek{at}charite.de


   Abstract

Background: The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a central regulator of myocardial fatty acid (FA) metabolism implicated in the pathogenesis of heart failure.

Aims: To characterize PPAR{alpha} regulation in human dilated cardiomyopathy (DCM), we studied the expression of cardiac PPAR{alpha}, cardiac carnitine palmitoyl-transferase I (CPT-1), a major PPAR{alpha} target gene, and of the cardiac glucose transporter GLUT-4 in patients with DCM.

Methods: Left ventricular biopsies were taken from patients with DCM (n=16) and control subjects (n=15), and mRNA expression was quantitated using real-time PCR (SYBR®Green) and protein expression was measured by Western immunoblotting.

Results: Left ventricular PPAR{alpha} mRNA levels were significantly increased in the DCM group compared to the control group (136±25.4% vs. control, p<0.01). Consistently, DCM patients had a significantly higher cardiac CPT-1 mRNA expression (147±51% vs. control, p<0.05) compared to the control group. Cardiac GLUT-4 expression was similar in both groups.

Conclusion: Elevated cardiac PPAR{alpha} levels followed by an induction of cardiac CPT-1 expression may result in increased fatty acid metabolism for cardiac energy production in DCM, suggesting a specific cardiac metabolic program in human DCM compared to other types of cardiomyopathy.

Key Words: Peroxisome proliferator-activated receptor alpha • Dilated cardiomyopathy • Fatty acids • Cardiac metabolism

Received March 11, 2005; Revised July 20, 2005; Accepted September 6, 2005


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