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 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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Li RC,Tao J,Guo YB,Wu HD,Liu RF,Bai Y,Lv ZZ,Luo GZ,Li LL,Wang M,Yang HQ,Gao W,Han QD,Zhang YY,Wang XJ,Xu M,Wang SQdoi
10.1161/CIRCRESAHA.112.300806subject
Has Abstractpub_date
2013-02-15 00:00:00pages
601-5issue
4eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.112.300806journal_volume
112pub_type
杂志文章abstract::The transverse tubular system (t-system) of cardiac muscle is a structure that allows rapid propagation of excitation into the cell interior. Using 2-photon molecular excitation microscopy and digital image-processing methods, we have obtained a comprehensive overview of the t-system of rat ventricular myocytes in liv...
journal_title:Circulation research
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更新日期:1995-12-01 00:00:00
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