Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice.

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Version: author
Serval ID
serval:BIB_0114E768F0AF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice.
Journal
Journal of the American Heart Association
Author(s)
Quattrocelli M., Crippa S., Montecchiani C., Camps J., Cornaglia A.I., Boldrin L., Morgan J., Calligaro A., Casasco A., Orlacchio A., Gijsbers R., D'Hooge J., Toelen J., Janssens S., Sampaolesi M.
ISSN
2047-9980 (Electronic)
ISSN-L
2047-9980
Publication state
Published
Issued date
2013
Volume
2
Number
4
Pages
e000284
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR-669a downregulation has been linked to the severe DCM progression displayed by Sgcb-null dystrophic mice. However, the impact of long-term overexpression of miR-669a on muscle structure and functionality of the dystrophic heart is yet unknown.
METHODS AND RESULTS: Here, we demonstrate that intraventricular delivery of adeno-associated viral (AAV) vectors induces long-term (18 months) miR-669a overexpression and improves survival of Sgcb-null mice. Treated hearts display significant decrease in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR-669a treatment increases sarcomere organization, reduces ventricular atrial natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM markers. Furthermore, long-term miR-669a overexpression significantly reduces adverse remodeling and enhances systolic fractional shortening of the left ventricle in treated dystrophic mice, without significant detrimental consequences on skeletal muscle wastage.
CONCLUSIONS: Our findings provide the first evidence of long-term beneficial impact of AAV-mediated miRNA therapy in a transgenic model of severe, chronic MD-associated DCM.
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2013 16:59
Last modification date
20/08/2019 12:23
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