Ericsson Madelene, Andersson Kristin B, Amundsen Brage H, Torp Sverre H, Sjaastad Ivar, Christensen Geir, Sejersted Ole M, Ellingsen Øyvind
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.
J Appl Physiol (1985). 2010 May;108(5):1311-20. doi: 10.1152/japplphysiol.01133.2009. Epub 2010 Feb 18.
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.
多项证据表明，肌浆（内质）网ATP酶2型（SERCA2）对于维持心肌钙处理和心脏泵功能至关重要。因此，预计SERCA2丰度降低会降低工作能力和最大摄氧量（VO2max），并限制对运动训练的反应。为了验证这一假设，我们比较了Serca2基因心脏敲除小鼠（SERCA2 KO）和对照小鼠（SERCA2 FF）的VO2max和运动能力。我们还确定了高强度有氧运动训练是否可以改变对VO2max和运动能力的影响。在Serca2基因敲除2周后开始以VO2max的85 - 90%进行跑步机跑步，并持续4周。每周在代谢室中测量VO2max和最大跑步速度。在轻度麻醉下通过超声心动图评估心脏功能。在久坐不动的SERCA2 KO小鼠中，有氧能力降低了50%，跑步速度降低了28%，而训练后的SERCA2 KO小鼠尽管VO2max降低了36%，仍能够维持最大跑步速度。在SERCA2 FF小鼠中，训练使VO2max和最大跑步速度均增加，而久坐组则无变化。两种基因型的小鼠经训练后左心室尺寸均未改变。相比之下，训练诱导SERCA2 KO小鼠右心室肥大。总之，SERCA2蛋白对于维持心脏泵功能和运动能力至关重要。然而，尽管VO2max大幅下降，SERCA2 KO小鼠在接受运动训练后仍能够维持最大跑步速度。
