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
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
收藏
页码:9 / 14
页数:6
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