title: High-intensity exercise training in mice with cardiomyocyte-specific disruption of Serca2.
abstract: Several lines of evidence indicate that the sarco(endo)plasmic reticulum ATPase type 2 (SERCA2) is essential for maintaining myocardial calcium handling and cardiac pump function. Hence, a reduction in SERCA2 abundance is expected to reduce work performance and maximal oxygen uptake (VO2max) and to limit the response to exercise training. To test this hypothesis, we compared VO2max and exercise capacity in mice with cardiac disruption of Serca2 (SERCA2 KO) with control mice (SERCA2 FF). We also determined whether the effects on VO2max and exercise capacity could be modified by high-intensity aerobic exercise training. Treadmill running at 85-90% of VO2max started 2 wk after Serca2 gene disruption and continued for 4 wk. VO2max and maximal running speed were measured weekly in a metabolic chamber. Cardiac function was assessed by echocardiography during light anesthesia. In sedentary SERCA2 KO mice, the aerobic capacity was reduced by 50% and running speed by 28%, whereas trained SERCA2 KO mice were able to maintain maximal running speed despite a 36% decrease in VO2max. In SERCA2 FF mice, both VO2max and maximal running speed increased by training, while no changes occurred in the sedentary group. Left ventricle dimensions remained unchanged by training in both genotypes. In contrast, training induced right ventricle hypertrophy in SERCA2 KO mice. In conclusion, the SERCA2 protein is essential for sustaining cardiac pump function and exercise capacity. Nevertheless, SERCA2 KO mice were able to maintain maximal running speed in response to exercise training despite a large decrease in VO2max.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, and Department of Medical Imaging, St. Olavs Hospital, Olav Kyrres gate 9, NO-7489 Trondheim, Norway.
authors.forename: Madelene
authors.initials: M
authors.lastname: Ericsson
authors.forename: Kristin B
authors.initials: KB
authors.lastname: Andersson
authors.forename: Brage H
authors.initials: BH
authors.lastname: Amundsen
authors.forename: Sverre H
authors.initials: SH
authors.lastname: Torp
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: D000222:Adaptation, Physiological; D000818:Animals; D020013:Calcium Signaling; D017079:Exercise Tolerance / Q000235:genetics; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000201:enzymology*; D010101:Oxygen Consumption / Q000235:genetics; D005082:Physical Exertion; D012333:RNA, Messenger / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left
chemical_list: D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse