In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 112, No. 4 ( 2013-02-15), p. 601-605
Abstract:
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 and Results: 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.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.112.300806
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2013
detail.hit.zdb_id:
1467838-X
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