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J Hypertens. 2012 Apr;30(4):778-86. doi: 10.1097/HJH.0b013e3283505101.

Overexpression of coupling factor 6 attenuates exercise-induced physiological cardiac hypertrophy by inhibiting PI3K/Akt signaling in mice.

Author information

1
Department of Cardiology, Hirosaki University Graduate School of Medicine, 5-Zaifu-Cho, Hirosaki, Japan.

Abstract

BACKGROUND:

Regular exercise improves systolic cardiac dysfunction through Akt cascade-mediated physiological hypertrophy in congestive heart failure. Tissue acidosis impairs Akt cascade, and coupling factor 6 induces tissue acidosis via activation of ecto-F(1)F(o) complex. We tested the hypothesis that coupling factor 6 attenuates physiological cardiac hypertrophy induced by exercise and its benefit in mice.

METHODS AND RESULTS:

Adult wild-type mice (n = 20) and coupling factor 6-overexpressing transgenic mice (n = 20) were divided into two groups with or without 4-week exercise consisting of 90-min swimming twice daily. Left ventricular posterior wall and interventricular septum thicknesses were increased by 0.12 ± 0.1 and 0.16 ± 0.1 mm, respectively, after 4-week swimming in wild-type mice (both P < 0.01), but unchanged in transgenic mice. Fractional shortening was increased from 37 ± 1 to 41 ± 1% after 4-week swimming in wild-type mice (P < 0.05), whereas it was unchanged in transgenic. The insulin-like growth factor 1 (IGF-1) receptor protein and its phosphorylated form in the heart were both increased by 1.83 ± 0.23 and 1.83 ± 0.09 times, respectively, after 4-week swimming in wild-type mice (both P < 0.05), but were unchanged in transgenic. Downstream phosphoinsulin receptor substrate 1, phosphoinositide 3-kinase, and phospho-Akt were increased by 2.22 ± 0.22, 1.78 ± 0.31, and 2.24 ± 0.49 times, respectively, in wild-type mice (all P < 0.05), but were unchanged in transgenic. Restoration of phospho-Akt by IGF-1 injection recovered left ventricular hypertrophy and systolic function after 4-week swimming in transgenic.

CONCLUSION:

Overexpression of coupling factor 6 attenuates exercise-induced physiological cardiac hypertrophy by downregulating Akt signaling, thereby cancelling its benefit for cardiac function in mice. Reduction in coupling factor 6 level seems to be useful for drawing the exercising effects on cardiac function.

PMID:
22306848
DOI:
10.1097/HJH.0b013e3283505101
[Indexed for MEDLINE]

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