title: In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.
abstract: BACKGROUND
  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.
  
  
  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.
authors: College of Life Sciences, Peking University, Beijing 100871, China.
authors: Rong-Chang
authors: RC
authors: Li
authors: Jin
authors: J
authors: Tao
authors: Yun-Bo
authors: YB
authors: Guo
authors: Hao-Di
authors: HD
authors: Wu
authors: Rui-Feng
authors: RF
authors: Liu
authors: Yan
authors: Y
authors: Bai
authors: Zhi-Zhen
authors: ZZ
authors: Lv
authors: Guan-Zheng
authors: GZ
authors: Luo
authors: Lin-Lin
authors: LL
authors: Li
authors: Meng
authors: M
authors: Wang
authors: Hua-Qian
authors: HQ
authors: Yang
authors: Wei
authors: W
authors: Gao
authors: Qi-De
authors: QD
authors: Han
authors: You-Yi
authors: YY
authors: Zhang
authors: Xiu-Jie
authors: XJ
authors: Wang
authors: Ming
authors: M
authors: Xu
authors: Shi-Qiang
authors: SQ
authors: Wang
mesh_terms: D000818:Animals; D001020:Aortic Stenosis, Subvalvular / Q000150:complications; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D056966:Excitation Contraction Coupling / Q000187:drug effects*; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
chemical_list: D020746:Calcium Channels, L-Type; D008565:Membrane Proteins; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D016376:Oligonucleotides, Antisense; D019837:Ryanodine Receptor Calcium Release Channel; C412507:junctophilin