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Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model

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Abstract

Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, partially replacing the ventricular essential light chains (VLC-1). This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts.

To study the functional importance of hALC-1 in the intact perfused heart, we generated a transgenic rat model (TGR) overexpressing hALC-1 in the heart. Twelve-week-old TGR rats expressed 17±4 μg hALC-1 per mg of whole SDS-soluble protein. Their perfused heart contractility parameters were evaluated using the Langendorff preparation. Expression of hALC-1 was accompanied by statistically significant improvements (P<0.001) in the contractile parameters of the hearts of the TGR compared to the age matched control (WKY) animals, represented by increases from 20.8±2.3 to 45.1±3.6 mmHg/g heart weight in the developed left ventricular pressure, 1,035.7±89.8 to 2,181±135.4 mmHg/s in the contraction rate, and 713±60.2 to 1,364±137.4 mmHg/s in the relaxation rate in the WKY and the TGR groups respectively. Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure.

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Acknowledgements

We are grateful to Steffen Lutter and Rosemarie Barnow for their excellent technical assistance. This work was supported by the DFG (Deutsche Forschungsgemeinschaft) Mo 362/22-1, Graduiertenkolleg 754 and VACSERA (The Egyptian Holding Company for Biological Products and Vaccines), 9-02-20/1/02.

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Authors and Affiliations

  1. Max-Delbrück-Center for Molecular Medicine (MDC), Molecular Muscle Physiology, Robert-Rössle-Strasse 10, 13125, Berlin, Germany

    Ahmed Ihab Abdelaziz, Holger Bartsch, Daria Petzhold, Wolfgang-Peter Schlegel, Monika Kott, Michael Bader, Hannelore Haase & Ingo Morano

  2. Humboldt University, Charité, Berlin, Germany

    Ingo Morano

  3. Institute of Human Genetics, Humboldt University, Charité, Berlin, Germany

    Jadranka Segaric, Ingo Seefeldt & Joachim Klose

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  1. Ahmed Ihab Abdelaziz
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  2. Jadranka Segaric
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Correspondence to Ahmed Ihab Abdelaziz.

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Abdelaziz, A.I., Segaric, J., Bartsch, H. et al. Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model. J Mol Med 82, 265–274 (2004). https://doi.org/10.1007/s00109-004-0525-4

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  • DOI: https://doi.org/10.1007/s00109-004-0525-4

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