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

Item Type:Article
Title:Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model
Creators Name:Abdelaziz, A.I. and Segaric, J. and Bartsch, H. and Petzhold, D. and Schlegel, W. and Kott, M. and Seefeldt, I. and Klose, J. and Bader, M. and Haase, H. and Morano, I.
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.
Keywords:Contractility, Essential Myosin Light Chains, Heart, Transgenic Rats, Animals, Rats
Source:Journal of Molecular Medicine
Page Range:265-274
Date:1 January 2004
Official Publication:https://doi.org/10.1007/s00109-004-0525-4
PubMed:View item in PubMed

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