Abstract 11444: Overexpression of Coupling Factor 6 Attenuates Exercise-Induced Physiological Cardiac Hypertrophy By Inhibiting Pi3k/akt Signaling in Mice
Background: Regular exercise improves cardiac dysfunction through Akt cascade-mediated physiological hypertrophy in congestive heart failure. Tissue acidosis impairs Akt cascade. We reported that coupling factor 6 (CF6) induces tissue acidosis via activation of ecto-F1Fo complex. We also reported the increase in circulating CF6 level in various cardiovascular diseases. We examined whether CF6 attenuates physiological cardiac hypertrophy induced by exercise and its benefit in mice.
Methods and Results: Wild type (WT, n=20) and CF6-overexpressing transgenic mice (TG, n=20) were assigned to 2 groups: One group underwent 4-week exercise of 90 minutes swimming twice daily and the other did not. Thus, the mice were divided into 4 group, WT-non-swim, WT-swim, TG-non-swim, and TG-swim. Baseline body weight (BW), heart rate (HR), blood pressures, and echocardiographic findings were all similar among 4 groups. BW was unchanged after 4-week exercise in both WT-swim and TG-swim, but increased in WT-non-swim and TG-non-swim. HR did not change in both WT-non-swim and TG-non-swim, but it decreased in WT-swim and TG-swim. After 4-week exercise, left ventricular posterior wall and interventricular septum thicknesses increased by 0.16±0.10mm and 0.12±0.10mm (both p<0.01) in WT-swim, but was unchanged in TG-swim. Fractional shortening increased from 37±1% to 41±1% in WT-swim (p<0.05), whereas it was unchanged in TG-swim. Gene expression of insulin-like growth factor 1 (IGF-1) in the heart did not differ among 4 groups. IGF-1 receptor protein and its phosphoryated form in the heart increased by 1.83±0.23 and 1.83±0.09 times, respectively, in WT-swim compared with WT-non-swim (both p<0.05), but were unchanged in TG. Downstream phospho-insulin receptor substrate 1, phosphoinositide 3-kinase, and phospho-Akt increased by 2.22±0.22, 1.78±0.31, and 2.24±0.49 times, respectively, in WT-swim compared with WT-non-swim (all p<0.05), but were unchanged in TG.
Conclusions: Overexpression of CF6 attenuates exercise-induced physiological cardiac hypertrophy by down-regulating Akt signaling, and thereby cancells the benefit of exercise for cardiac function in mice. Reduction in CF6 level seems to be useful for drawing the exercising effects on cardiac function.
- © 2011 by American Heart Association, Inc.