Up-regulation of PPARgamma in myocardial infarction.
BACKGROUND
Peroxisome proliferator activated receptors (PPARs) are key regulators for cardiac energy metabolism after myocardial injury. We hypothesized, that PPARs are regulated in myocardial infarction (MI) and their activity is modulated by angiotensin receptor blockers (ARBs).


METHODS
Following induction of MI, male rats were treated with placebo or the ARB irbesartan for three weeks. PPARalpha, beta/delta and gamma protein expression and gene expression of PPAR target genes and glucose transporters were measured. PPARgamma-protein expression was analyzed by immunofluorescence.


RESULTS
MI decreased LVP and dp/dtmax and increased LVEDP, this effect was counteracted by irbesartan. PPARalpha and PPARbeta/delta protein expression was not altered in MI and was not affected by irbesartan. PPARgamma protein content was increased in the infarcted area and localized to cardiac myocytes and fibroblasts. In parallel, expression of CTGF was increased 10-fold in the infarcted zone. PPAR target genes (CD36, MCAD, ACO and GLUT4) were significantly decreased in infarcted tissue, and this was unaffected by irbesartan. However, CD36 and ACO in the non-infarcted areas were up-regulated by irbesartan.


CONCLUSIONS
Endogenous up-regulation of PPARgamma in MI is insufficient to counteract the decrease in metabolic genes, but parallels an increase in the profibrotic mediator CTGF. Irbesartan increases fatty acid oxidating enzymes after MI independent of PPARgamma regulation.
Fliegner
Daniela
D
Cardiovascular Disease in Women, Charité, Center for Cardiovascular Research, Charité, University of Medicine Berlin, Germany.
Westermann
Dirk
D
Riad
Alexander
A
Schubert
Carola
C
Becher
Eva
E
Fielitz
Jens
J
Tschöpe
Carsten
C
Regitz-Zagrosek
Vera
V
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D015854:Up-Regulation
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; C526316:CCN2 protein, rat; D018955:CD36 Antigens; C008132:Cd36 protein, rat; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D018110:Receptors, Lipoprotein; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D013777:Tetrazoles; D055513:Connective Tissue Growth Factor; D000077405:Irbesartan