, Volume 113, Issue 10, pp 2473-2486
Date: 28 Jun 2013

Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway

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Abstract

Purpose

Swimming exercise leads to a nonpathological, physiological left ventricular hypertrophy. However, the potential molecular mechanisms are unknown. We investigated the role of microRNAs (miRNA) regulating the cardiac signal cascades were studied in exercised rats.

Methods

Female Wistar rats were assigned into two groups: (1) sedentary control (SC), (2) swimming exercise (SE). The rats in the SE group completed a 1-h swimming exercise, 5 times/week/8-week with 5 % body overload. miRNA, phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3α), phosphatase and tensin homolog (PTEN) and tuberous sclerosis complex 2 (TSC2) gene expression analysis were performed by real-time PCR in heart muscle. Moreover, we assessed cardiac protein expression of ERK1/2, PI3K/AKT/mTOR, PTEN and TSC2.

Results

Cardiac phosphoser473-AKT and phosphoSer2448-mTOR were, respectively, increased by 46 and 38 % in the SE group when compared with SC group. miRNAs-21, 144, and 145 were, respectively, up-regulated in the SE group (152 %, 128, and 101 % relative increases), but miRNA-124 was decreased by 38 %. In SE group, PIK3α (targeted by miRNA-124) gene expression increased by 213 %, and Pten (targeted by miRNAs-21 and 144), and TSC2 (targeted by miRNA-145) were, respectively, decreased by 51 and 55 %. In addition, the swimming exercise increased protein levels of PIK3α (36 %) and phosphoThr1462-TSC2 (48 %), while it decreased PTEN (37 %) and TSC2 (22 %), which induced activation of PI3K/AKT/mTOR signaling pathway.

Conclusion

These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, changing the expression of specific miRNAs targeting the PIK3/AKT/mTOR signaling pathway and its negative regulators.

Communicated by Martin Flueck.