title: Exercise training before cardiac-specific Serca2 disruption attenuates the decline in cardiac function in mice.
abstract: In the heart, function of the sarco(endo)plasmic Ca(2+)-ATPase (SERCA2) is closely linked to contractility, cardiac function, and aerobic fitness. SERCA2 function can be increased by high-intensity interval training, whereas reduced SERCA2 abundance is associated with impaired cardiac function. The working hypothesis was, therefore, that exercise training before cardiomyocyte-specific disruption of the Serca2 gene would delay the onset of cardiac dysfunction in mice. Before Serca2 gene disruption by tamoxifen, untreated SERCA2 knockout mice (Serca2(flox/flox) Tg-αMHC-MerCreMer; S2KO), and SERCA2 FF control mice (Serca2(flox/flox), S2FF) were exercise trained by high-intensity interval treadmill running for 6 wk. Both genotypes responded to training, with comparable increases in maximal oxygen uptake (Vo(2max); 17%), left ventricle weight (15%), and maximal running speed (40%). After exercise training, cardiac-specific Serca2 gene disruption was induced in both exercise trained and sedentary S2KO mice. In trained S2KO, cardiac function decreased less rapidly than in sedentary S2KO. Vo(2max) remained higher in trained S2KO the first 15 days after gene disruption. Six weeks after Serca2 disruption, cardiac output was higher in trained compared with sedentary S2KO mice. An exercise-training program attenuates the decline in cardiac performance induced by acute cardiac Serca2 gene disruption, indicating that mechanisms other than SERCA2 contribute to the favorable effect of exercise training.
authors.affiliation: Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Madelene
authors.initials: M
authors.lastname: Ericsson
authors.forename: Cecilie
authors.initials: C
authors.lastname: Sjåland
authors.forename: Kristin B
authors.initials: KB
authors.lastname: Andersson
authors.forename: Ivar
authors.initials: I
authors.lastname: Sjaastad
authors.forename: Geir
authors.initials: G
authors.lastname: Christensen
authors.forename: Ole M
authors.initials: OM
authors.lastname: Sejersted
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Ellingsen
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D005838:Genotype; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology*; D010641:Phenotype; D005082:Physical Exertion; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse