| Title | In Vivo Suppression of MicroRNA-24 Prevents the Transition Toward Decompensated Hypertrophy in Aortic-Constricted Mice |
| Authors | Li, Rong-Chang Tao, Jin Guo, Yun-Bo Wu, Hao-Di Liu, Rui-Feng Bai, Yan Lv, Zhi-Zhen Luo, Guan-Zheng Li, Lin-Lin Wang, Meng Yang, Hua-Qian Gao, Wei Han, Qi-De Zhang, You-Yi Wang, Xiu-Jie Xu, Ming Wang, Shi-Qiang |
| Affiliation | Peking Univ, Hosp 3, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. Chinese Acad Sci, Key Lab Genet Network Biol, Inst Genet & Dev Biol, Beijing, Peoples R China. |
| Keywords | Ca2+ signaling hypertrophic cardiomyopathy hypertrophy heart failure myocardial contraction HEART-FAILURE CARDIAC-HYPERTROPHY MYOCARDIAL-INFARCTION CELLS CALCIUM CHANNEL MUSCLE |
| Issue Date | 2013 |
| Publisher | circulation research |
| Citation | CIRCULATION RESEARCH.2013,112,(4),601-+. |
| Abstract | Rationale: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca2+ 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 Ca2+ 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 Ca2+ channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca2+ 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. (Circ Res. 2013; 112:601-605.) |
| URI | http://hdl.handle.net/20.500.11897/309326 |
| ISSN | 0009-7330 |
| DOI | 10.1161/CIRCRESAHA.112.300806 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第三医院 生命科学学院 |
