© 2005 European Society of Cardiology
Cardiac PPAR
expression in patients with dilated cardiomyopathy
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
) is a central regulator of myocardial fatty acid (FA) metabolism implicated in the pathogenesis of heart failure.
Aims: To characterize PPAR
regulation in human dilated cardiomyopathy (DCM), we studied the expression of cardiac PPAR
, cardiac carnitine palmitoyl-transferase I (CPT-1), a major PPAR
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
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
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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