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Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling?

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Abstract

Ventricular remodeling following myocardial infarction (MI) includes myocardial hypertrophy, a process requiring increased protein synthesis and sarcomere assembly. The anti-hypertrophic effect of MuRF1/MafBx, both muscle-specific E3-ubiquitin ligases, has been demonstrated in animal experiments and in cultured cardiomyocytes. We assessed MuRF1/MAFbx expression in myocardium remote of recently (<2 weeks) infarcted regions (MI), compared with patients undergoing coronary artery bypass surgery, with normal systolic function and without previous infarction (control or Con). Left ventricular myocardial biopsies were obtained from the contralateral normal zone in MI (n = 14) patients and from the Con (n = 12) group. MuRF-1/MAFbx expression was assessed using RT-PCR and Western blot (WB). In addition, the myocardial expression of TNF-α was measured (RT-PCR) and troponin I, β-myosin and phosphorylated Akt/Akt (pAkt/Akt) were quantified (WB). MuRF1 and MAFbx expression (mRNA and protein level) were significantly reduced in biopsies from MI patients. TNF-α was significantly higher in MI and exhibited a negative correlation with MuRF1 and MAFbx. The expression of troponin I and cardiomyocyte size were increased in MI in comparison to Con, whereas β-myosin expression was not altered. When compared with Con, pAkt/Akt was elevated. The results of the present study suggest that the atrogenes MuRF1/MAFbx are involved in regulating the hypertrophic response, characteristic of the early post-infarction remodeling phase. Reduced expression of MuRF1 and MAFbx in the myocardium might permit hypertrophy, which is supported by the elevation of troponin I. A regulatory role of TNF-α needs to be confirmed in further experiments.

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Acknowledgment

We would like to thank Nicole Urban and Tina Fischer for excellent technical assistance; and Siegfried Labeit for providing the MuRF1 specific antibody. This work was supported by Fonds voor Wetenschappelijk onderzoek (FWO)-Flanders (VC, clinical postdoctoral fellow) and by the Deutsche Forschungsgemeinschaft (LI946/3-1).

Conflict of interest statement

None declared.

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Authors and Affiliations

  1. Department of Cardiology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium

    Viviane M. Conraads , Christiaan J. Vrints, Vicky Y. Hoymans, Emeline M. Van Craenenbroeck, Johan Bosmans, Marc J. Claeys & Paul Van Herck

  2. Center of Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium

    Viviane M. Conraads , Christiaan J. Vrints, Vicky Y. Hoymans & Emeline M. Van Craenenbroeck

  3. Department of Cardiac Surgery, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium

    Inez E. Rodrigus

  4. Department of Cardiology, University Leipzig-Heart Centre Leipzig, Leipzig, Germany

    Axel Linke, Gerhard Schuler & Volker Adams

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  1. Viviane M. Conraads
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Correspondence to Viviane M. Conraads .

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Conraads , V.M., Vrints, C.J., Rodrigus, I.E. et al. Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling? . Basic Res Cardiol 105, 219–226 (2010). https://doi.org/10.1007/s00395-009-0068-5

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  • DOI: https://doi.org/10.1007/s00395-009-0068-5

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