Journal article

Therapeutic silencing of miR-652 restores heart function and attenuates adverse remodeling in a setting of established pathological hypertrophy

Bianca C Bernardo, Sally S Nguyen, Catherine E Winbanks, Xiao-Ming Gao, Esther JH Boey, Yow Keat Tham, Helen Kiriazis, Jenny YY Ooi, Enzo R Porrello, Sindhu Igoor, Colleen J Thomas, Paul Gregorevic, Ruby CY Lin, Xiao-Jun Du, Julie R McMullen

FASEB JOURNAL | FEDERATION AMER SOC EXP BIOL | Published : 2014

Abstract

Expression of microRNA-652 (miR-652) increases in the diseased heart, decreases in a setting of cardioprotection, and is inversely correlated with heart function. The aim of this study was to assess the therapeutic potential of inhibiting miR-652 in a mouse model with established pathological hypertrophy and cardiac dysfunction due to pressure overload. Mice were subjected to a sham operation or transverse aortic constriction (TAC) for 4 wk to induce hypertrophy and cardiac dysfunction, followed by administration of a locked nucleic acid (LNA)-antimiR-652 (miR-652 inhibitor) or LNA control. Cardiac function was assessed before and 8 wk post-treatment. Expression of miR-652 increased in heart..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council Future Fellowship


Awarded by National Health and Medical Research Council


Awarded by National Heart Foundation


Funding Acknowledgements

This study was funded by National Health and Medical Research Council of Australia project grant 586603 (to J.R.M and R.C.Y.L), and also supported in part by the Victorian Government's Operational Infrastructure Support Program. X.J.D. and J.R.M. are National Health and Medical Research Council Senior Research Fellows (APP1043026 and 586604). J.R.M., R.C.Y.L., and P.G. are supported by an Australian Research Council Future Fellowship (FT0001657), a University of New South Wales Vice Chancellor Research Fellowship, and a R.D. Wright Biomedical Research Fellowship from the National Health and Medical Research Council (1046782), respectively. E.R.P. is supported by grants and fellowships from the National Health and Medical Research Council and the National Heart Foundation (APP1033815 and 635530). The authors declare no conflicts of interest.