Cardiac PPARα expression in patients with dilated cardiomyopathy

Background: The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a central regulator of myocardial fatty acid (EA) 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 PPARa 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 (R) Green) and protein expression was measured by Western immunoblotting. Results: Left ventricular PPARa 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. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.