Abstract 19868: Mirna-17-3p Controls Exercise-induced Cardiac Growth
Aims: Endurance exercise has been proved to be a stimulus for cardiac growth and it can induce cardiac hypertrophy and cardiomyocyte proliferation. Although genes and transcriptional factors responsible for that has been well-established, little is known about the potential role of microRNAs (miRNAs, miRs) in this physiological process. The miR-17-92 cluster has been reported to promote cell proliferation and play anti-apoptotic roles in tumor cells. This study aims at investigating the role of miR-17-92 cluster or its member in exercise-induced cardiac growth.
Methods: Endurance exercise was induced by swimming the mice for 3 weeks. Using quantitative reverse transcription polymerase chain reactions (RT-PCRs), members in miR-17-92 clusters were determined and miR-17-3p was found to be significantly up-regulated. The expression levels of miR-17-3p in ventricular tissue of mice subjected to transaortic constriction (TAC) and DCM patients were also determined using RT-PCRs. In cultured cardiomyocytes, the effects of forced-expression of miR-17-3p in cell size and proliferation were checked using α-Actinin and EdU or KI-67 staining. Western blotting and RT-PCRs were used to determine the expression levels of tissue inhibitor of metalloproteinase-3 (TIMP-3) and proteins in AKT/PI3K pathway in isolated cardiomyocytes.
Results: miR-17-3p was up-regulated in mouse swimming exercise model while decreased in the ventricular tissue of DCM patients and TAC mice. In isolated cardiomyocytes, miR-17-3p induced cardiomyocytes hypertrophy and proliferation. MiR-17-3p was found to increase the AKT/PI3K pathway, contributing to cardiomyocytes hypertrophy. In addition, TIMP-3 was identified as a target gene responsible for cardiaomyocyte proliferation.
Conclusions: MiR-17-3p is responsible for cardiac growth induced by exercise.
Author Disclosures: J. Shi: None. Q. Xuan: None. W. Sun: None. Y. Ji: None. H. Wang: None. S. Fu: None. J. Xiao: None. X. Kong: None.
- © 2014 by American Heart Association, Inc.