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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.
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页码:9 / 14
页数:6
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