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

Authors

  • A.I. Abdelaziz
  • J. Segaric
  • H. Bartsch
  • D. Petzhold
  • W. Schlegel
  • M. Kott
  • I. Seefeldt
  • J. Klose
  • M. Bader
  • H. Haase
  • I. Morano

Journal

  • Journal of Molecular Medicine

Citation

  • J Mol Med 82 (4): 265-274

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.


DOI

doi:10.1007/s00109-004-0525-4