Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function
Bianca C Bernardo, Xiao-Ming Gao, Catherine E Winbanks, Esther JH Boey, Yow Keat Tham, Helen Kiriazis, Paul Gregorevic, Susanna Obad, Sakari Kauppinen, Xiao-Jun Du, Ruby CY Lin, Julie R McMullen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2012
MicroRNAs are dysregulated in a setting of heart disease and have emerged as promising therapeutic targets. MicroRNA-34 family members (miR-34a, -34b, and -34c) are up-regulated in the heart in response to stress. In this study, we assessed whether inhibition of the miR-34 family using an s.c.-delivered seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiR (LNA-antimiR-34) can provide therapeutic benefit in mice with preexisting pathological cardiac remodeling and dysfunction due to myocardial infarction (MI) or pressure overload via transverse aortic constriction (TAC). An additional cohort of mice subjected to MI was given LNA-antimiR-34a (15-mer) to inhibit miR-34a alone as a co..View full abstract
Awarded by National Health and Medical Research Council
Awarded by Australia Research Council Future Fellowship
We thank Dr. P. Kantharidis for advice with the luciferase assays and N. Jennings for assistance with echocardiography. This study was funded by National Health and Medical Research Council Project Grants 586603 (to J.R.M. and R.C.Y.L.) and 586649 (to P.G.) 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 (317808 and 586604). J.R.M., R.C.Y.L., and P. G. are supported by an Australia Research Council Future Fellowship (FT0001657), a University of New South Wales Vice Chancellor Research Fellowship, and a Pfizer Australia Senior Research Fellowship, respectively.