title: MiRNAs with apoptosis regulating potential are differentially expressed in chronic exercise-induced physiologically hypertrophied hearts.
abstract: Physiological cardiac hypertrophy is an adaptive mechanism, induced during chronic exercise. As it is reversible and not associated with cardiomyocyte death, it is considered as a natural tactic to prevent cardiac dysfunction and failure. Though, different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy, their role during physiological hypertrophy is largely unexplored. Hence, this study is aimed at revealing the global expression profile of miRNAs during physiological cardiac hypertrophy. Chronic swimming protocol continuously for eight weeks resulted in induction of physiological hypertrophy in rats and histopathology revealed the absence of tissue damage, apoptosis or fibrosis. Subsequently, the total RNA was isolated and small RNA sequencing was executed. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during physiological hypertrophy. The expression profile of the significantly differentially expressed miRNAs was validated by qPCR. In silico prediction of target genes by miRanda, miRdB and TargetScan and subsequent qPCR analysis unraveled that miRNAs including miR-99b, miR-100, miR-19b, miR-10, miR-208a, miR-133, miR-191a, miR-22, miR-30e and miR-181a are targeting the genes that primarily regulate cell proliferation and cell death. Gene ontology and pathway mapping showed that the differentially expressed miRNAs and their target genes were mapped to apoptosis and cell death pathways principally via PI3K/Akt/mTOR and MAPK signaling. In summary, our data indicates that regulation of these miRNAs with apoptosis regulating potential can be one of the major key factors in determining pathological or physiological hypertrophy by controlling fibrosis, apoptosis and cell death mechanisms.
authors: Cardiac Hypertrophy Laboratory, Department of Molecular Biology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors: Subbiah
authors: S
authors: Ramasamy
authors: Cardiac Hypertrophy Laboratory, Department of Molecular Biology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors: Ganesan
authors: G
authors: Velmurugan
authors: Cardiac Hypertrophy Laboratory, Department of Molecular Biology, School of Biological Sciences, Madurai Kamaraj University, Madurai, Tamilnadu, India.
authors: K
authors: K
authors: Shanmugha Rajan
authors: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors: Tharmarajan
authors: T
authors: Ramprasath
authors: Department of Plant Pathology, Regional Research Station, Tamilnadu Agricultural University, Krishangiri, Tamilnadu, India.
authors: Krishnan
authors: K
authors: Kalpana
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D006332:Cardiomegaly / Q000235:genetics* / Q000503:physiopathology*; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D063990:Gene Ontology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010805:Physical Conditioning, Animal; D017208:Rats, Wistar; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs