Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction

被引：60

作者：

Frantz, S ^{[1
]}

Hu, K ^{[1
]}

Widder, J ^{[1
]}

Bayer, B ^{[1
]}

Witzel, CC ^{[1
]}

Schmidt, I ^{[1
]}

Galuppo, P ^{[1
]}

Strotmann, J ^{[1
]}

Ertl, G ^{[1
]}

Bauersachs, J ^{[1
]}

机构：

[1] Univ Wurzburg, Med Klin, D-97080 Wurzburg, Germany

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2004年 / 141卷 / 01期

关键词：

infarction; heart failure; glitazone; cytokine; collagen;

D O I：

10.1038/sj.bjp.0705585

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1 Peroxisome proliferator activated receptor gamma (PPARgamma) 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 PPARgamma agonists. Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice. 2 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. 3 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, endsystolic area, placebo sham 9.6 +/- 1.3 vs placebo MI 14.4 +/- 2.5 mm(2)). However, there was no difference between the placebo and pioglitazone groups (week 6, end-systolic area, pioglitazone MI 14.8 +/- 2.9 mm(2), P = NS vs placebo). 4 Moreover, there were no changes in metabolic parameters, inflammation, and collagen deposition. Endothelial function in the aorta was not changed by PPARgamma activation. 5 In conclusion, PPARgamma 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.

引用

页码：9 / 14

页数：6

共 35 条

[21] Peroxisome proliferator-activated receptors (PPARs) in the vessels wall - new regulators of gene expression in vascular cells [J].