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ES cells overexpressing microRNA-1 attenuate apoptosis in the injured myocardium

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Abstract

MicroRNAs (miRs) are small, single-stranded, noncoding RNA’s involved in post-transcriptional negative gene regulation. Recent investigations have underscored the integral role of miRs in various biological processes including innate immunity, cell-cycle regulation, metabolism, differentiation, and cell death. In the present study, we overexpressed miR-1, a muscle-specific miR, in embryonic stem cells (miR-1-ES cells), transplanted them into the infarcted myocardium, and evaluated their impact on cardiac apoptosis and function. We provide evidence demonstrating reduced apoptosis following transplantation of miR-1-ES cells 4 weeks post-myocardial infarction as compared to respective controls assessed by TUNEL staining and a capsase-3 activity assay. Moreover, we show significant elevation in p-Akt levels and diminished PTEN levels in hearts transplanted with miR-1-ES cells as determined by enzyme-linked immunoassays. Finally, using echocardiography, we reveal mice receiving miR-1-ES cell transplantation post-myocardial infarction had significantly improved fractional shortening and ejection fraction compared with respective controls. Our data suggest transplanted miR-1-ES cells inhibit apoptosis, mediated through the PTEN/Akt pathway, leading to improved cardiac function in the infarcted myocardium.

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Acknowledgments

This work was supported in part from grants from the National Institutes of Health [1R01HL090646-01, and 5R01HL094467-02 to DKS].

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Authors and Affiliations

  1. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida BLVD, Room 224, Orlando, FL, 32816, USA

    Carley Glass & Dinender K. Singla

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  1. Carley Glass
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  2. Dinender K. Singla
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Correspondence to Dinender K. Singla.

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Glass, C., Singla, D.K. ES cells overexpressing microRNA-1 attenuate apoptosis in the injured myocardium. Mol Cell Biochem 357, 135–141 (2011). https://doi.org/10.1007/s11010-011-0883-5

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  • DOI: https://doi.org/10.1007/s11010-011-0883-5

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