In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.
Circ Res
; 112(4): 601-5, 2013 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-23307820
ABSTRACT
RATIONALE During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes. OBJECTIVE:
To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes. METHODS ANDRESULTS:
In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction, but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in L-type Ca(2+) channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca(2+) transients. Further studies showed that antagomir treatment stabilized junctophilin-2 expression and protected the ultrastructure of T-tubule-sarcoplasmic reticulum junctions from disruption.CONCLUSIONS:
MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos Antissenso
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Hipertrofia Ventricular Esquerda
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Sinalização do Cálcio
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Miócitos Cardíacos
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MicroRNAs
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Acoplamento Excitação-Contração
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Insuficiência Cardíaca
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2013
Tipo de documento:
Article