title: Human atrial myosin light chain 1 expression attenuates heart failure.
abstract: Most patients with hypertrophic cardiomyopathy and congenital heart diseases express the atrial essential myosin light chains (ALC-1) in their ventricles, replacing the ventricular essential light chains (VLC-1). VLC-1/ALC-1 isoform shift is correlated with increases in cardiac contractile parameters of a transgenic rat model overexpressing hALC-1 in the heart (TGR/hALC-1) compared to normal WKY rats. To investigate, whether the benefical effects of the hALC-1 on cardiac contractility could attenuate contractile failure of the overloaded heart, aortocaval shunt operations of 9-10 weeks old WKY and TGR/hALC-1 were performed. 5 weeks later, both animals groups were sacrificed for analysis of cardiac contraction and transgene expression. Control animals were operated but remained normal body and heart weights. The whole heart contractility parameters were evaluated using the Langendorff heart preparation. Shunt-operated TGR/hALC-1 and WKY rats developed comparable levels of cardiac hypertrophy which was associated with significant reduction of contractile parameters of the Langendorff hearts. However, the decline of cardiac contractility was less pronounced in shunt-operated TGR/hALC-1 compared to shunt-operated WKY. In fact, developed left ventricular pressure as well as maximal velocity of pressure development and relaxation were significantly higher in shunt-operated TGR/hALC-1 as compared to shunt-operated WKY. Expression of hALC-1 was 17 microg/mg whole SDS-protein in control (sham-operated) controls and declined significantly to 14 microg/mg whole SDS-protein in hypertrophied TGR/hALC-1. These results demonstrate that the expression of hALC-1 could have a beneficial effect on the overloaded hypertrophied heart.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: Ahmed Ihab
authors.initials: AI
authors.lastname: Abdelaziz
authors.forename: Ines
authors.initials: I
authors.lastname: Pagel
authors.forename: Wolfgang-Peter
authors.initials: WP
authors.lastname: Schlegel
authors.forename: Monika
authors.initials: M
authors.lastname: Kott
authors.forename: Jan
authors.initials: J
authors.lastname: Monti
authors.forename: Hannelore
authors.initials: H
authors.lastname: Haase
authors.forename: Ingo
authors.initials: I
authors.lastname: Morano
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D009202:Cardiomyopathies / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006325:Heart Atria / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D010477:Perfusion; D051381:Rats
chemical_list: D018994:Myosin Light Chains; C491915:hALC-1 protein, human