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

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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., Segaric, J., Bartsch, H., Petzhold, D., Schlegel, W., Kott, M., Seefeldt, I., Klose, J., Bader, M., 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
ISSN:	0946-2716
Publisher:	Springer
Volume:	82
Number:	4
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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