在活体内抑制microRNA-24可避免主动脉缩窄小鼠转变为失代偿性肥大

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice
作者:Li, R.-C.a, Tao, J.a, Guo, Y.-B.a, Wu, H.-D.a, Liu
机构: 北京大学生命科学学院生物膜与膜生物工程国家重点实验室
期刊: CIRC RES2013年2月4,15期112卷

State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China

Rationale: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca 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 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 channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca 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. © 2012 American Heart Association, Inc.

Wang, S.-Q.; State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China; email:wsq@pku.edu.cn

通讯作者:Wang, S.-Q.; State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China; email:wsq@pku.edu.cn
学科代码:血液病学   关键词:vivo_inhibition_of_mirna
来源: Scopus
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