Published in:
British Journal of Pharmacology, 141 (2004) 1, Seite 9-14
Language:
English
DOI:
10.1038/sj.bjp.0705585
ISSN:
0007-1188;
1476-5381
Origination:
Footnote:
Description:
Peroxisome proliferator activated receptor γ (PPARγ) has been implicated in several cellular pathways assumed to beneficially affect heart failure progression. In contrast, population‐based studies demonstrate an increased incidence of heart failure in patients treated with PPARγ agonists. Therefore, we examined the effect of pioglitazone, a PPARγ agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice.Mice were treated with placebo or pioglitazone (20 mg kg−1 by gavage) from week 1 to week 6 after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at weeks 1, 3, and 6.Over 6 weeks, there was no difference in mortality (placebo 12%, pioglitazone 10%). Echocardiography showed significant left ventricular dilatation in animals with MI (week 6, end‐systolic area, placebo sham 9.6±1.3 vs placebo MI 14.4±2.5 mm2). However, there was no difference between the placebo and pioglitazone groups (week 6, end‐systolic area, pioglitazone MI 14.8±2.9 mm2, P=NS vs placebo).Moreover, there were no changes in metabolic parameters, inflammation, and collagen deposition. Endothelial function in the aorta was not changed by PPARγ activation.In conclusion, PPARγ activation did not adversely affect left ventricular remodeling and survival in mice with chronic MI. However, we were also not able to identify a protective effect of pioglitazone.British Journal of Pharmacology (2004) 141, 9–14. doi:10.1038/sj.bjp.0705585