Cardiac PPARalpha expression in patients with dilated cardiomyopathy.
BACKGROUND
The peroxisome proliferator-activated receptor alpha (PPARalpha) is a central regulator of myocardial fatty acid (FA) metabolism implicated in the pathogenesis of heart failure.


OBJECTIVE
To characterize PPARalpha regulation in human dilated cardiomyopathy (DCM), we studied the expression of cardiac PPARalpha, cardiac carnitine palmitoyl-transferase I (CPT-1), a major PPARalpha 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 PPARalpha 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.


CONCLUSIONS
Elevated cardiac PPARalpha 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.
Schupp
Michael
M
Center for Cardiovascular Research, CCR, Institute of Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, CCM, Hessischestr. 3-4, 10115 Berlin, Germany.
Kintscher
Ulrich
U
Fielitz
Jens
J
Thomas
Jennifer
J
Pregla
Reinhard
R
Hetzer
Roland
R
Unger
Thomas
T
Regitz-Zagrosek
Vera
V
D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D005260:Female; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis
D051275:Glucose Transporter Type 4; D047493:PPAR alpha; D012333:RNA, Messenger; D002334:Carnitine O-Palmitoyltransferase