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Activation of PPARγ by pioglitazone does not attenuate left ventricular hypertrophy following aortic banding in rats

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Abstract

Sustained left ventricular hypertrophy (LVH) accelerates cardiac dysfunction and heart failure. Previous reports have suggested that activation of the peroxisome proliferator-activated receptor γ (PPARγ)-dependent pathway is involved in development of cardiac hypertrophy. Thiazolidinediones (TZDs) such as pioglitazone activate PPARγ and are clinically used as antidiabetics. Given inconsistent reports regarding effects of TZDs on LVH, we examined in the present study the influence of pioglitazone on LVH in a rat model of aortic banding. Aortic banding was induced in rats by clipping the ascending aorta. Animals received pioglitazone (3 mg/kg/day) or placebo. Echocardiographic, hemodynamic, histological, and biochemical measurements were performed after 2 and 4 weeks. Pressure gradient was comparable between pioglitazone- and placebo-treated animals after 2 and 4 weeks. Left ventricular function was not different between the groups. In sham as well as in banded animals, LV/body weight ratio was increased in pioglitazone- as compared to placebo-treated animals after 2 and 4 weeks. Furthermore, an increase in myocyte size and atrial natriuretic factor was observed in pioglitazone- compared to placebo-treated animals 4 weeks after aortic banding as well. The results of this study demonstrate that activation of PPARγ via pioglitazone does not protect the myocardium from pressure overload-induced LVH in a rat model of aortic banding. The findings rather indicate a pro-hypertrophic effect of pioglitazone treatment after aortic banding.

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Acknowledgements

The work presented herein was supported by the Deutsche Forschungsgemeinschaft (HA 2959/2-2) to SEH.

The authors would like to acknowledge the expert technical assistance of Silvia Harrack. We also want to thank Karl Heinz Weiss for helpful comments to the manuscript.

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Authors and Affiliations

  1. Department of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Celine S. Weiss, Marco Hagenmüller, Martina Pichler, Sebastian Münz, Marco Ochs, Sebastian J. Buss, Raffi Bekeredjian, Hugo A. Katus & Stefan E. Hardt

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  1. Celine S. Weiss
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  2. Marco Hagenmüller
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  3. Martina Pichler
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  4. Sebastian Münz
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  5. Marco Ochs
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Correspondence to Stefan E. Hardt.

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Weiss, C.S., Hagenmüller, M., Pichler, M. et al. Activation of PPARγ by pioglitazone does not attenuate left ventricular hypertrophy following aortic banding in rats. Naunyn-Schmied Arch Pharmacol 381, 285–295 (2010). https://doi.org/10.1007/s00210-009-0488-7

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  • DOI: https://doi.org/10.1007/s00210-009-0488-7

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