Document Detail


Therapeutic silencing of miR-652 restores heart function and attenuates adverse remodeling in a setting of established pathological hypertrophy.
MedLine Citation:
PMID:  25145628     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 hearts subjected to TAC compared to sham surgery (2.9-fold), and this was suppressed by ∼95% in LNA-antimiR-652-treated TAC mice. Inhibition of miR-652 improved cardiac function in TAC mice (fractional shortening:29±1% at 4 wk post-TAC compared to 35±1% post-treatment) and attenuated cardiac hypertrophy. Improvement in heart function was associated with reduced cardiac fibrosis, less apoptosis and B-type natriuretic peptide gene expression, and preserved angiogenesis. Mechanistically, we identified Jagged1 (a Notch1 ligand) as a novel direct target of miR-652. In summary, these studies provide the first evidence that silencing of miR-652 protects the heart against pathological remodeling and improves heart function.-Bernardo, B. C., Nguyen, S. S., Winbanks, C. E., Gao, X.-M., Boey, E. J. H., Tham, Y. K., Kiriazis, H., Ooi, J. Y. Y., Porrello, E. R., Igoor, S., Thomas, C. J., Gregorevic, P., Lin, R. C. Y., Du, X.-J., McMullen, J. R. Therapeutic silencing of miR-652 restores heart function and attenuates adverse remodeling in a setting of established pathological hypertrophy.
Authors:
Bianca C Bernardo; Sally S Nguyen; Catherine E Winbanks; Xiao-Ming Gao; Esther J H Boey; Yow Keat Tham; Helen Kiriazis; Jenny Y Y Ooi; Enzo R Porrello; Sindhu Igoor; Colleen J Thomas; Paul Gregorevic; Ruby C Y Lin; Xiao-Jun Du; Julie R McMullen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-21
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  -     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© FASEB.
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