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Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
3/25/2007-3/28/2007
Hannover, Germany
MATRIX METALLOPROTEINASES ACT AS REPRESSOR OF HYPERTROPHY IN VENTRICULAR CARDIOMYOCYTES OF RAT
Abstract number: P17-L6-08
Heger1 J, Schiegnitz1 E, Muktheshwar1 G, Asif1 AR, Piper1 HM, Euler1 G
1Physiologisches Institut, Justus-Liebig Universitt, Gieen
Hypertrophic growth represents a protection for the heart after increased load. Progression of hypertrophy can result in decompensation and deterioration of heart function. In the last years factors have been identified that can protect against the development of hypertrophic growth. In this study we have identified matrix metalloproteinases (MMP) as repressors of hypertrophy. Under the assumption that cardiomyocytes (CM) express transcription factors (TF) which can reduce hypertrophic growth, CM were transformed with oligonucleotides (ON) containing binding sites for different factors. CM transformed with an ON with no homology to a known binding sequence induced enhanced growth. Sequencing of the protein that binds to ON in EMSAs identified the MMP component hemopexin. Expression of hemopexin-mRNA in CM could be verified by realtime PCR. Transformation of CM with hemopexin antisense ON increased protein synthesis rate. So did the MMP-inhibitor TAPI (50 mM). Conclusion:: MMPs are expressed in CM and act as repressors for hypertrophic growth. Besides the familiar impact of MMPs on cardiac remodelling by changing the extracellular matrix, a direct effect of MMPs on hypertrophic growth could now be demonstrated. A further characterization of this mechanism is required, to strengthen the capacity of the heart to deal with excessive growth.
To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 189, Supplement 653 :P17-L6-08